Multimodal Imaging Core

The Multimodal Imaging Core provides services to investigators locally, regionally, and nationally, encompassing scales that range from cellular to whole-animal imaging. The goal of the Core is to support the research of investigators in qualitative and quantitative imaging applications and to assist with study design, data interpretation, grant submissions, and to conduct preclinical and IND-enabling studies.

In vivo imaging services provided by Core faculty and trained professionals includes ultrasound imaging, optical imaging, positron emission tomography (PET), computed tomography (CT), and total-body PET with the primate mini-EXPLORER, in addition to radiochemistry and pharmacokinetic analyses.

Dedicated faculty and staff are responsible for imaging services, radiotracer synthesis, administrative support, day-to-day operational management, computer support, preventive and routine maintenance, quality assurance and quality control.

The Core also provides slide sectioning and staining services specific to nonhuman primates and whole slide scanning.

The Core provides services, expertise, and training, including advanced imaging applications that address innovative research questions across the lifespan. The in vivo imaging program provides a unique depth and breadth of services offered for high-resolution brain and total-body imaging that meets a broad spectrum of investigator needs. The Core has a long-standing history in providing research support to investigators, including assistance with extramural grant applications.

Innovative techniques and procedures have provided a means for investigators to incorporate non-invasive ultrasound-related techniques and procedures in their research programs, and to use non-surgical ultrasound-guided methods to develop and study new monkey models of human disease. Ultrasound imaging includes a spectrum of applications during pregnancy. Normative prenatal growth parameters are well established, including mean data tables, predicted values, and 95% confidence intervals for multiple head, abdominal, and limb measures, in addition to early gestational biometrics. Ultrasound is also used extensively as an adjunct for guiding the delivery of agents into various fetal compartments and for collecting fetal specimens.

Highly innovative methods for bioluminescence imaging have been developed and applied for a spectrum of gene therapy and stem cell transplantation studies.

A GE Discovery® 610 PET/CT and total-body PET scanner are used for an array of studies including protocols that have focused on radiolabeled antibodies and assessing cell and viral trafficking; fetal development using a combined ultrasound and CT imaging protocol; biodistribution of iodinated proteins; and inflation CT scans. Studies also address tissue engineered constructs with scaffolds and stem/progenitor cells to tailor the construct.

Emerging applications for PET, particularly for stem and progenitor cell trafficking and engraftment, requires the ability to image very low activity source distributions. The Core has developed methods for radiolabeling of cells for regenerative medicine purposes, and adapted these techniques to radiolabel viruses and monitor trafficking and viral sanctuaries.

New radiotracers are available in the Core (through partnership with the UC Davis Center for Molecular and Genomic Imaging) including 11C-PK11195 and 18F-PBR111 that bind to the translocator protein (TSPO) to monitor inflammation, 18F-FMT for studying dopamine synthesis, and 11C-PIB for amyloid imaging.

The Core has developed a complement of techniques including those used to explore the pharmacokinetics of novel radiopharmaceuticals with high performance liquid chromatography (HPLC). A laboratory is dedicated for this purpose, and staff provide the expertise for these services.

Quantitative Image Analysis (QIA) refers to the standardized extraction of meaningful, quantitative information from imaging data and uses computational algorithms. QIA methods ensure imaging biomarkers are reproducible and less subjective, and can provide imaging biomarkers for future application in human clinical trials.

Imaging plays a critical role in precision medicine, which is focused on early diagnostics and personalized treatments. The Core plays an important role in precision imaging through novel functional imaging techniques and developing new imaging biomarkers and tools.

The Core has the world’s first total-body PET scanner, EXPLORER, designed for humans that allows all the tissues and organs to be imaged simultaneously. In vivo imaging capabilities and novel models are provided by faculty in the School of Medicine and College of Engineering, that are members of the Reproductive Sciences and Regenerative Medicine Unit. The Core partnership with the Center for Molecular and Genomic Imaging, a campus core facility with a biomedical cyclotron, provides on-site synthesis of custom radiotracers for the Core.

Select publications from Multimodal Imaging Core activities

Baker CA, Swainson L, Lin DL, Wong S, Hartigan-O’Connor DJ, Lifson JD, Tarantal AF, and McCune JM. Exposure to SIV in utero results in reduced viral loads and altered responsiveness to postnatal challenge. Sci Transl Med. 2015;7(300):300ra125. PMCID: PMC5100009

Bakkour S, Baker CA, Tarantal AF, Wen L, Busch MP, Lee TH, and McCune JM. Analysis of maternal microchimerism in rhesus monkeys (Macaca mulatta) using real-time quantitative PCR amplification of MHC polymorphisms. Chimerism. 2014;5(1):6-15. PMCID: PMC3988117

Batchelder CA, Duru N, Lee CI, Baker CA, Swainson L, McCune JM, and Tarantal AF. Myeloid-lymphoid ontogeny in the rhesus monkey (Macaca mulatta). Anat Rec (Hoboken). 2014;297(8):1392-406. PMCID: PMC4120262

Batchelder CA, Martinez ML, Duru N, Meyers FJ, and Tarantal AF. Three dimensional culture of human renal cell carcinoma organoids. PLoS One. 2015;10(8):e0136758. PMCID: PMC4552551

Batchelder CA, Martinez ML, and Tarantal AF. Natural scaffolds for renal differentiation of human embryonic stem cells for kidney tissue engineering. PLoS One. 2015;10(12):e0143849. PMCID: PMC4672934

Berg E, Roncali E, and Cherry SR. Optimizing light transport in scintillation crystals for time-of-flight PET: an experimental and optical Monte Carlo simulation study. Biomed Opt Express. 2015;6(6):2220-30. PMCID: PMC4473755

Berg E, Roncali E, Hutchcroft W, Qi J, and Cherry SR. Improving depth, energy and timing estimation in PET detectors with deconvolution and maximum likelihood pulse shape discrimination. IEEE Trans Med Imaging. 2016; 35(11):2436-46. PMCID: PMC5119913

Berg E, Roncali E, Kapusta M, Du J, and Cherry SR. A combined time-of-flight and depth-of-interaction detector for total-body positron emission tomography. Med Phys. 2016;43(2):939-50. PMCID: PMC4733082

Carbonaro Sarracino D, Tarantal AF, Lee CC, Martinez M, Jin X, Wang X, Hardee CL, Geiger S, Kahl CA, and Kohn DB. Effects of vector backbone and pseudotype on lentiviral vector-mediated gene transfer: studies in infant ADA-deficient mice and rhesus monkeys. Mol Ther. 2014;22(10):1803-16. PMCID: PMC4428412

Chaffin CL, Latham KE, Mtango NR, Midic U, and VandeVoort CA. Dietary sugar in healthy female primates perturbs oocyte maturation and in vitropreimplantation embryo development. Endocrinology. 2014; 155(7):2688-95. PMCID: PMC4060180

Conlon T, Mah C, Pacak C, Rucker Henninger M, Erger K, Jorgensen M, Lee C, Tarantal AF, and Byrne BJ. Transfer of therapeutic genes into fetal rhesus monkeys using recombinant adeno-associated type 1 viral vectors.  Hum Gene Ther Clin Dev. 2016;27(4):152-9. PMCID: PMC5310237

Corti M, Cleaver B, Clément N, Conlon TJ, Faris KJ, Wang G, Benson J, Tarantal AF, Fuller D, Herzog RW, and Byrne BJ. Evaluation of readministration of a recombinant adeno-associated virus vector expressing acid alpha-glucosidase in Pompe disease: Preclinical to clinical planning. Hum Gene Ther Clin Dev. 2015; 26(3):185-93. PMCID: PMC4606909

Du J, Yang Y, Bai X, Judenhofer MS, Berg E, Di K, Buckley S, Jackson C, and Cherry SR. Characterization of large-area SiPM array for PET applications. IEEE Trans Nucl Sci. 2016;63(1):8-16. PMCID: PMC4281963

Engle JR, Machado CJ, Permenter MR, Vogt JA, Maurer AP, Bulleri AM, and Barnes CA. Network patterns associated with navigation behaviors are altered in aged nonhuman primates. J Neurosci. 2016;36(48):12217-27. PMCID: PMC5148220

Gong K, Cherry SR, and Qi J. On the assessment of spatial resolution of PET systems with iterative image reconstruction. Phys Med Biol. 2016;61(5):N193-202. PMCID: PMC4890626

Hinde K, Muth C, Maninger N, Ragen BJ, Larke RH, Jarcho MR, Mendoza SP, Mason WA, Ferrer E, Cherry SR, Fisher-Phelps ML, and Bales KL. Challenges to the pair bond: Neural and hormonal effects of separation and reunion in a monogamous primate. Front Behav Neurosci. 2016;10:221. PMCID: PMC5107580

Hinderer C, Bell P, Louboutin JP, Zhu Y, Yu H, Lin G, Choa R, Gurda BL, Bagel J, O’Donnell P, Sikora T, Ruane T, Wang P, Tarantal AF, Casal ML, Haskins ME, and Wilson JM. Neonatal systemic AAV induces tolerance to CNS gene therapy in MPS I dogs and nonhuman primates. Mol Ther. 2015;23(8):1298-307. PMCID: PMC4817868

Kwon SI, Ferri A, Gola A, Berg E, Piemonte C, Cherry SR, and Roncali E. Reaching 200-ps timing resolution in a time-of-flight and depth-of-interaction positron emission tomography detector using phosphor-coated crystals and high-density silicon photomultipliers. J Med Imaging (Bellingham). 2016;3(4):043501. PMCID: PMC5120149

Kwon SI, Gola A, Ferri A, Piemonte C, and Cherry SR. Bismuth germanate coupled to near ultraviolet silicon photomultipliers for time-of-flight PET. Phys Med Biol. 2016;61(18):L38-L47. PMCID: PMC5056849

Nicol LE, O’Brien TD, Dumesic DA, Grogan T, Tarantal AF, and Abbott DH. Abnormal infant islet morphology precedes insulin resistance in PCOS-like monkeys. PLoS One. 2014;9(9):e106527. PMCID: PMC4160158

Qu Y, Frazer LC, O’Connell CM, Tarantal AF, Andrews CW Jr, O’Connor SL, Russell AN, Sullivan JE, Poston TB, Vallejo AN, and Darville T. Comparable genital tract infection, pathology, and immunity in rhesus macaques inoculated with wild-type or plasmid-deficient Chlamydia trachomatis serovar D. Infect Immun. 2015; 83(10):4056-67. PMCID: PMC4567646

Tai DS, Hu C, Lee CC, Martinez M, Cantero G, Kim EH, Tarantal AF, and Lipshutz GS. Development of operational immunologic tolerance with neonatal gene transfer in nonhuman primates: preliminary studies. Gene Ther. 2015;22(11):923-30. NIHMSID: NIHMS867303

VandeVoort CA, Gerona RR, Vom Saal FS, Tarantal AF, Hunt PA, Hillenweck A, and Zalko D. Maternal and fetal pharmacokinetics of oral radiolabeled and authentic bisphenol A in the rhesus monkey. PLoS One. 2016; 11(12):e0165410. PMCID: PMC5145146

VandeVoort CA, Grimsrud KN, Midic U, Mtango N, and Latham KE. Transgenerational effects of binge drinking in a primate model: implications for human health. Fertil Steril. 2015;103(2):560-9. PMCID: PMC4314404