Julie C. Price

Julie C. Price is an American physicist and Professor of Radiology at Harvard Medical School as well as the Director of PET Pharmacokinetic Modeling at the Athinoula A. Martinos Center at Massachusetts General Hospital. Price is a leader in the study and applications of quantitative positron emission tomography (PET) and led the first fully quantitative pharmacokinetic evaluations of Pittsburgh compound-B (PIB), one of the most widely used PET ligands for imaging amyloid beta plaques. As a principal investigator at Harvard and continuing collaborator with the University of Pittsburgh, Price innovates novel PET methods for imaging biological markers of health and disease such as glucose metabolism, protein expression, neurotransmitter system function, and tau and amyloid beta plaque burden.

Julie C. Price
NationalityAmerican
Alma materUniversity of Wisconsin-Madison
Johns Hopkins University
National Institutes of Health
Known forPharmacokinetic analyses of PIB PET ligand
Awards2016 Alavi–Mandell Award
Scientific career
FieldsRadiology, Physics
InstitutionsHarvard Medical School

Early life and education

Price attended the University of Wisconsin-Madison for her undergraduate degree.[1] She majored in physics and graduated with a Bachelors of Science in 1982.[1] Upon completion of her bachelors, Price stayed at the University of Wisconsin-Madison to pursue her Master’s in Medical Physics.[1] She worked in the Radiation Calibration Service as a project specialist during her Master’s where she explored the efficacy of diode dosimeters in the detection of radiation in mailed radiotherapy.[2] Upon completion of her Master’s in 1985, Price worked as Physics Research Assistant in the Diagnostic Radiology Department at the Mayo Clinic in Rochester, Minnesota.[1] She led studies to assess the level of radiation exposure to the fetus from multislice CT scans.[3]

Price then pursued her graduate studies at Johns Hopkins University within the School of Hygiene and Public Health in Baltimore, Maryland.[1] She focused her research in Environmental Health Sciences and Radiation Health Sciences.[1] Towards the end of her graduate degree in 1990, Price began working with Marc A. Feldman and J. James Frost in the Department of Radiology in Johns Hopkins School of Medicine where she began to quantify and measure kinetics of various receptors in the human and non-human primate brain.[4] She quantified opiate receptor concentrations and affinity in the human brain using Diprenorphine and PET imaging[5] and then used Single Photon Emission Tomography to measure Benzodiazepine receptor concentration and affinity in the brains of non-human primates.[6] For her thesis work, she used a novel approach to measure benzodiazepine receptor concentration combining tracer kinetic modeling of flumazenil in PET imaging.[4]

Price then completed her postdoctoral work at the National Institutes of Health in the Department of PET and Nuclear Medicine where she pioneered a novel method to reduce the transmission noise in 18F-FDG cardiac emission images.[7] Her innovative method uses a model that sharpens the peaks of the measured attenuation histograms of the images to minimize noise while preventing too much smoothing of the data.[7]

Career and research

Following her postdoctoral training, Price was recruited to the University of Pittsburgh in 1994 as a physicist and Assistant Professor in the PET Facility and Department of Radiology at the University of Pittsburgh Medical Center.[8] In 2002, Price was promoted to Associate Professor and became the Director of PET Imaging, Methodology, and Statistics Core at the University of Pittsburgh, a position she held until 2016.[9] In 2010, she became a Full Professor in the Department of Radiology and in 2013, became a Full Professor in the Department of Biostatistics.[1] During her 14 year tenure, she was awarded over 40 National Institutes of Health grants to foster the investigation of the pharmacokinetic properties of PET ligands for use in human disease diagnosis and health assessment.[10]

In 2016, Price became a Visiting Professor of Radiology at Harvard Medical School’s Martinos Center for Biomedical Imaging as well as an Investigator in the Department of Radiology at the Massachusetts General Hospital.[1] She was also appointed Director of PET Pharmacokinetic Modeling at the Massachusetts General Hospital/Health Sciences Technology Martinos Center in Boston.[1] As of 2018, Price began collaborating with and serving as a Senior Research Scientist in the Massachusetts Alzheimer’s Disease Research Center.[11] She uses her expertise in PET imaging to guide a team towards establishing novel methods to diagnosis AD through imaging of Tau and Amyloid Beta plaque deposits.[11] She continues to collaborate with her previous institutions including the Waisman Center at the University of Wisconsin-Madison[12] and the University of Pittsburgh.[13] Price is also an associate editor of the Journal of Cerebral Blood Flow and Metabolism, a leading journal in the field.[14]

Price is also the Principal Investigator of the Price Lab at Harvard Medical School where she focuses on innovating and improving PET imaging methods for early diagnosis of human disease.[15] She leads a variety of projects such as applying PET imaging to assess epigenetic changes in Huntington’s Disease and Parkinson’s Disease and developing novel diagnostic methods to measure pathological Tau deposition in the human brain through PET imaging.[16] Her research also addresses race-based differences in disease as she explores the mechanisms of altered peripheral glucose uptake in African American women.[16] She also uses PET imaging to assess the outcomes of meditation on chronic pain and migraines by tracking neuroinflammation using novel PET ligands.[16]

Early evaluation of PiB in PET imaging

While at the University of Pittsburgh, Price played an integral role in the kinetic evaluation of the Pittsburgh Compound B, a radioactive analog of thioflavin T, and its use in imaging amyloid beta plaques and neurofibrillary tangles in the brain.[17] At the time that Price began working at Pittsburgh, the interest in using PET imaging for diagnosis of Alzheimer’s Disease was just beginning to rise. Price’s colleagues William E. Klunk and Chester A. Mathis developed a novel PET ligand, which was soon called Pittsburgh compound-B (PIB), which bound to neuritic or amyloid beta plaques, thus effectively allowing observation of plaque load in the brain.[18] When Price joined the faculty, she created a quantitative imaging method to measure the load of amyloid beta plaques in the brain based on PIB signal.[18] She found that PIB retention was a stable and valid marker of AD which was a critical first step in the field of using this method for diagnosis and therapeutic guidance for patients with AD.[18] Price later helped to discover that PIB is selective to human plaques and cannot be used to assess plaque deposition in mouse models.[19] Price also led several follow-up studies to confirm the optimal time window and experimental designs for use of PIB in diagnosis of AD.[20]

Tau imaging

After pioneering the use of PET imaging in the tracking and assessment of amyloid beta burden in the brains of AD patients, Price sought to use PET imaging to observe the Tau burden in AD patients as Tau deposition has been shown to be associated with neurodegeneration in various diseases.[21] Price helped to improve the existing tools for PET imaging Tau by first debunking the idea that the common Tau PET ligand [F-18]AV-1451 aberrantly bind the choroid plexus leading to false positives.[22] Price and her team explored the possible presence of tau tangles in the epithelial cells that line the choroid plexus and found that in fact they do contain tangles and they are labelled by tau antibodies as well.[23] Price’s findings suggest that the previous reports of off target binding of [F-18]AV-1451 are actually just binding to brain boarder cells that are suffering from AD pathology.[23] In a 2019 paper, Price explored sex differences in tau deposition using the flortaucipir F18 PET ligand and they found that women had higher early tau deposition compared to men on an AD trajectory.[24]

Vascular risk factors in brain disease

In addition to neurodegeneration, Price was a founding researcher in the investigation of vascular abnormalities in psychiatric disease using PET imaging. Since PET imaging enables analysis of cerebral physiology, Price led a study exploring whether cerebral blood flow (CBF) to the brain is reduced in aging.[25] Price and her team found that when they corrected for the dilution effect of age-related atrophy, they did not observed a decrease in CBF and future studies should be sure to account for dilution effects to improving the accuracy of brain measurements.[25] Price has also explored changes in CBF in women with bulimia nervosa and found that there was an inverse relationship between the length of recovery and the level of CBF suggesting that CBF might be a predictor of recovery.[26]

Awards and honors
  • 2016 Alavi–Mandell Awards for 2015 Scientific Article "Relative 11C-PiB Delivery as a Proxy of Relative CBF: Quantitative Evaluation Using Single-Session 15O-Water and 11C-PiB PET"[27]

Select publications
  • Price JC, Lopresti BJ, Mason NS, Holt DP, Meltzer CC, Smith GS, Gunn RN, Huang Y, Mathis CA. Analyses of [18F]altanserin bolus injection PET data II:  Consideration of radiolabeled metabolites in humans.  Synapse 2001; 41:11-21.[28]
  • Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, Holt DP, Meltzer CC, DeKosky ST,  Mathis CA. Kinetic Modeling of Amyloid Binding in Humans using PET Imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 2005; 25:1528-1547.[28]
  • Ziolko SK, Weissfeld LA, Klunk WE, Mathis CA, Hoge JA, Lopresti BJ, DeKosky ST, Price JC.   MH070729 Evaluation of Voxel-based Methods for the Statistical Analysis of PIB PET Amyloid Imaging Studies in Alzheimer’s Disease.  Neuroimage 2006; 33: 94-102.[28]
  • Innis RB, Cunningham VJ, Delforge J, Fujita M, Gunn RN, Holden J, Houle S, Huang S-C, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun M, Morris ED, Parsey R, Price J, Slifstein M, Sossi V, Suhara T, Votaw J, Wong DF, Carson RE. Consensus nomenclature for in vivo imaging of reversibly binding radioligands.  J Cereb Blood Flow Metab 2007 27:1533-1539.  PMID 17519979.[28]
  • Lois C, Gonzalez I, Johnson KA, Price JC. PET imaging of tau protein targets: a methodology perspective.  Brain Imaging Behav.  doi: 10.1007/s11682-018-9847-7[Epub].  PMID:  29497982[28]
  • Jagust WJ, Landau SM, Koeppe RA, Reiman EM, Chen K, Mathis CA, Price JC, Foster NL, Wang AY.  The Alzheimer's Disease Neuroimaging Initiative 2 PET Core: 2015.  Alzheimers Dement. July 2015;11(7):757-71. doi: 10.1016/j.jalz.2015.05.001. PMID 26194311; PMC4510459[28]
  • Jagust WJ, Landau SM, Koeppe RA, Reiman EM, Chen K, Mathis CA, Price JC, Foster NL, Wang AY.  The Alzheimer's Disease Neuroimaging Initiative 2 PET Core: 2015.  Alzheimers Dement. July 2015;11(7):757-71. doi: 10.1016/j.jalz.2015.05.001. PMID 26194311; PMC4510459[28]
  • Buckley RF, Mormino EC, Rabin JS, Hohman TJ, Landau S, Hanseeuw BJ, Jacobs HIL, Papp KV, Amariglio RE, Properzi MJ, Schultz AP, Kirn D, Scott MR, Hedden T, Farrell M, Price J, Chhatwal J, Rentz DM, Villemagne VL, Johnson KA, Sperling RA. Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured By Positron Emission Tomography in Clinically Normal Older Adults.   JAMA neurology. 2019; PMID 30715078[28]
  • Chen KT, Salcedo S, Chonde DB, Izquierdo-Garcia D, Levine MA, Price JC, Dickerson BC, Catana C. MR-assisted PET motion correction in simultaneous PET/MRI studies of dementia subjects.   J Magn Reson Imaging. 8 March 2018. doi: 10.1002/jmri.26000 [Epub].  PMID:  29517819.[28]
gollark: That is true, but it's cooler.
gollark: It's half the storage an ender chest thing would have.
gollark: No.
gollark: Same thing.
gollark: You need a big cobble machine which makes furnaces, like mine.

References
  1. "Julie Price, PhD | MGH/HST Martinos Center for Biomedical Imaging". www.nmr.mgh.harvard.edu. Retrieved June 2, 2020.
  2. La, DeWerd; J, Price; Jr, Cameron; Sj, Goetsch (October 1990). "Evaluation of a Commercial Diode Monitor for Mailed Quality Control of Therapy Units". International Journal of Radiation Oncology, Biology, Physics. 19 (4): 1053–7. doi:10.1016/0360-3016(90)90033-g. PMID 2211242.
  3. Jp, Felmlee; Je, Gray; Ml, Leetzow; Jc, Price (January 1990). "Estimated Fetal Radiation Dose From Multislice CT Studies". American Journal of Roentgenology. 154 (1): 185–90. doi:10.2214/ajr.154.1.2104708. PMID 2104708.
  4. Jc, Price; Hs, Mayberg; Rf, Dannals; Aa, Wilson; Ht, Ravert; B, Sadzot; Z, Rattner; A, Kimball; Ma, Feldman (July 1993). "Measurement of Benzodiazepine Receptor Number and Affinity in Humans Using Tracer Kinetic Modeling, Positron Emission Tomography, and [11C]flumazenil". Journal of Cerebral Blood Flow and Metabolism. 13 (4): 656–67. doi:10.1038/jcbfm.1993.84. PMID 8391018. S2CID 25903189.
  5. B, Sadzot; Jc, Price; Hs, Mayberg; Kh, Douglass; Rf, Dannals; Jr, Lever; Ht, Ravert; Aa, Wilson; Hn, Wagner (March 1991). "Quantification of Human Opiate Receptor Concentration and Affinity Using High and Low Specific Activity [11C]diprenorphine and Positron Emission Tomography". Journal of Cerebral Blood Flow and Metabolism. 11 (2): 204–19. doi:10.1038/jcbfm.1991.52. PMID 1847703. S2CID 38075132.
  6. M, Laruelle; A, Abi-Dargham; Z, Rattner; Ms, al-Tikriti; Y, Zea-Ponce; Ss, Zoghbi; Ds, Charney; J, Price; Jj, Frost (January 5, 1993). "Single Photon Emission Tomography Measurement of Benzodiazepine Receptor Number and Affinity in Primate Brain: A Constant Infusion Paradigm With [123I]iomazenil". European Journal of Pharmacology. 230 (1): 119–23. doi:10.1016/0014-2999(93)90421-d. PMID 8381354.
  7. Jc, Price; Sl, Bacharach; N, Freedman; Re, Carson (May 1996). "Noise Reduction in PET Attenuation Correction by Maximum Likelihood Histogram Sharpening of Attenuation Images". Journal of Nuclear Medicine. 37 (5): 786–94. PMID 8965146.
  8. "Brain's Serotonin System Declines With Age Shows UPMC Research". EurekAlert!. Retrieved June 2, 2020.
  9. Price, Julie. "Mapping Brain Structure and Function in AD". Grantome.
  10. "Grantome: Search". Grantome. Retrieved June 2, 2020.
  11. "KEEP IN MIND A newsletter for friends and supporters of the Massachusetts Alzheimer's Disease Research Center and The Memory Study" (PDF). madrc.org. Retrieved June 1, 2020.
  12. "Investigators and Staff / Natural History of Amyloid Deposition in Adults with Down Syndrome". www2.waisman.wisc.edu. Retrieved June 2, 2020.
  13. "RDAtlas". www.rdatlas.com. Retrieved June 2, 2020.
  14. "Journal of Cerebral Blood Flow & Metabolism". SAGE Publications Ltd. November 3, 2015. Retrieved June 2, 2020.
  15. "People – Price Lab". Retrieved June 2, 2020.
  16. "Ongoing Research – Price Lab". Retrieved June 2, 2020.
  17. We, Klunk; H, Engler; A, Nordberg; Bj, Bacskai; Y, Wang; Jc, Price; M, Bergström; Bt, Hyman; B, Långström (November 2003). "Imaging the Pathology of Alzheimer's Disease: Amyloid-Imaging With Positron Emission Tomography". Neuroimaging Clinics of North America. 13 (4): 781–9, ix. doi:10.1016/s1052-5149(03)00092-3. PMID 15024961.
  18. Jc, Price; We, Klunk; Bj, Lopresti; X, Lu; Ja, Hoge; Sk, Ziolko; Dp, Holt; Cc, Meltzer; St, DeKosky (November 2005). "Kinetic Modeling of Amyloid Binding in Humans Using PET Imaging and Pittsburgh Compound-B". Journal of Cerebral Blood Flow and Metabolism. 25 (11): 1528–47. doi:10.1038/sj.jcbfm.9600146. PMID 15944649. S2CID 8852082.
  19. We, Klunk; Bj, Lopresti; Md, Ikonomovic; Im, Lefterov; Rp, Koldamova; Ee, Abrahamson; Ml, Debnath; Dp, Holt; Gf, Huang (November 16, 2005). "Binding of the Positron Emission Tomography Tracer Pittsburgh compound-B Reflects the Amount of Amyloid-Beta in Alzheimer's Disease Brain but Not in Transgenic Mouse Brain". The Journal of Neuroscience. 25 (46): 10598–606. doi:10.1523/JNEUROSCI.2990-05.2005. PMC 6725842. PMID 16291932.
  20. Bj, Lopresti; We, Klunk; Ca, Mathis; Ja, Hoge; Sk, Ziolko; X, Lu; Cc, Meltzer; K, Schimmel; Nd, Tsopelas (December 2005). "Simplified Quantification of Pittsburgh Compound B Amyloid Imaging PET Studies: A Comparative Analysis". Journal of Nuclear Medicine. 46 (12): 1959–72. PMID 16330558.
  21. C, Lois; I, Gonzalez; Ka, Johnson; Jc, Price (April 2019). "PET Imaging of Tau Protein Targets: A Methodology Perspective". Brain Imaging and Behavior. 13 (2): 333–344. doi:10.1007/s11682-018-9847-7. PMC 6119534. PMID 29497982.
  22. Ikonomovic, Milos D.; Abrahamson, Eric E.; Price, Julie C.; Mathis, Chester A.; Klunk, William E. (August 2016). "[F-18]AV-1451 PET retention in choroid plexus: more than "off-target" binding". Annals of Neurology. 80 (2): 307–308. doi:10.1002/ana.24706. ISSN 0364-5134. PMC 4982815. PMID 27314820.
  23. Ikonomovic, Milos D.; Abrahamson, Eric E.; Price, Julie C.; Mathis, Chester A.; Klunk, William E. (August 2016). "[F-18]AV-1451 PET retention in choroid plexus: more than "off-target" binding". Annals of Neurology. 80 (2): 307–308. doi:10.1002/ana.24706. ISSN 0364-5134. PMC 4982815. PMID 27314820.
  24. Rf, Buckley; Ec, Mormino; Js, Rabin; Tj, Hohman; S, Landau; Bj, Hanseeuw; Hil, Jacobs; Kv, Papp; Re, Amariglio (May 1, 2019). "Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults". JAMA Neurology. 76 (5): 542–551. doi:10.1001/jamaneurol.2018.4693. PMC 6515599. PMID 30715078.
  25. Cc, Meltzer; Mn, Cantwell; Pj, Greer; D, Ben-Eliezer; G, Smith; G, Frank; Wh, Kaye; Pr, Houck; Jc, Price (November 2000). "Does Cerebral Blood Flow Decline in Healthy Aging? A PET Study With Partial-Volume Correction". Journal of Nuclear Medicine. 41 (11): 1842–8. PMID 11079492.
  26. Gk, Frank; Wh, Kaye; P, Greer; Cc, Meltzer; Jc, Price (November 20, 2000). "Regional Cerebral Blood Flow After Recovery From Bulimia Nervosa". Psychiatry Research. 100 (1): 31–9. doi:10.1016/s0925-4927(00)00069-x. PMID 11090723.
  27. "2016 Award Recipients - SNMMI". www.snmmi.org. Retrieved June 2, 2020.
  28. "My Bibliography - NCBI". www.ncbi.nlm.nih.gov. Retrieved June 2, 2020.
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