MSTPublications: August 2017
Congratulations to all of our MSTP students on their successful publications! Take a look at the great work our students are doing.
First Author Original Research:
Volumetric MRI thermometry using a three-dimensional stack-of-stars echo-planar imaging pulse sequence.
Jonathan SV, Grissom WA.
Magn Reson Med. 2017 Aug 7. doi: 10.1002/mrm.26862. [Epub ahead of print]
Temperature monitoring with magnetic resonance imaging (MRI) has enabled many emerging minimally invasive thermal therapies, including MR-guided focused ultrasound (MRgFUS). MRgFUS is a completely noninvasive method that uses an external transducer to focus high-power ultrasound into tissue for ablation, and has been used successfully in humans to treat uterine fibroids, bone metastasis-related pain, cancer, and deep brain tissue. MRI-derived temperature maps based on the proton resonance frequency (PRF) shift with temperature are predominantly used to guide MRgFUS treatment. However, most clinical MR thermometry implementations for transcranial MRgFUS only image a single 2D slice in order to maintain an adequate signal-to-noise ratio for temperature monitoring. While acoustic energy from MRgFUS is nominally focused to a single point in one slice, there is an ever-present risk that unintended heating may occur in the near- and far-fields of the ultrasound transducer. In this work, our lab proposed and validated a three-dimensional stack-of-stars echo-planar imaging MRI pulse sequence to measure temperature over a large brain volume. Our sequence enables volumetric brain coverage for MR thermometry at high spatiotemporal resolution. (By Sumeeth Jonathan, G3)
Toll-like receptor 4 deficiency alters nucleus accumbens synaptic physiology and drug reward behavior.
Kashima DT, Grueter BA.
Proc Natl Acad Sci U S A. 2017 Jul 31. pii: 201705974. doi: 10.1073/pnas.1705974114. [Epub ahead of print]
Read more about this publication here.
Drugs of abuse alter synaptic connections onto neurons in the nucleus accumbens (NAc). These changes are thought as causal for maladaptive drug-reward learning and behavior. While typically studied in a neuron-centric manner, there is evidence pointing towards the immune system influencing drug-associated behavior. In this paper, I examined the consequence of knocking out the innate immune molecule toll-like receptor 4. I found that mice lacking this protein exhibit altered synaptic properties in NAc neurons, specifically relating to NMDA glutamate receptors. This was associated with altered learning mechanisms and an attenuation in cocaine-reward behavior. Together, these results highlight an immunologic influence on synaptic physiology and drug-reward. (By Daniel Kashima, M3)
Loss of the melanocortin-4 receptor in mice causes dilated cardiomyopathy.
Litt MJ, Okoye GD, Lark D, Cakir I, Moore C, Barber MC, Atkinson J, Fessel J, Moslehi J, Cone RD.
Elife. 2017 Aug 22;6. pii: e28118. doi: 10.7554/eLife.28118.
Haploinsufficiency of the melanocortin-4 receptor (MC4R) is the most common monogenetic obesity syndrome in humans. This syndrome is associated with a reduction in autonomic tone, bradycardia, hyperinsulinemia and a reduced prevalence of obesity-associated hypertension. Thus, it has been assumed that melanocortin obesity syndrome may be protective with respect to obesity-associated cardiovascular disease. We showed that deletion of MC4R in mice caused a dilated cardiomyopathy characterized by reduced contractility and increased left ventricular diameter. This cardiomyopathy we observed is independent of obesity, as weight matched wild type mice are spared from systolic dysfunction. Mc4r-/- heart tissue further displayed ultrastructural abnormalities in mitochondrial morphology and cardiomyocyte organization. Remarkably, mitochondrial function testing of myocardial tissue from Mc4r-/- mice revealed increased ADP stimulated respiration. This is in contrast to the reduction in O2 consumption seen in other models of cardiomyopathy, as well as the reduction in whole animal energy expenditure detected in MC4R knockout animals by indirect calorimetry. However, we also showed that this increase in respiration correlates with increased reactive oxygen species, canonical mediators of tissue damage. Supporting our hypothesis, Mc4r-/- heart tissue displays a similar transcriptional profile to that of treatment with doxorubicin, a free radical generating chemotherapy agent. Furthermore, Mc4r+/- mice are hypersensitive to the cachexigenic side effects of doxorubicin treatment. Therefore, this study identifies MC4R deletion as a novel and potentially clinically important cause of heart failure. We hope to perform clinical studies on patients with MC4R deficiency in the near future. (By Michael Litt, M3)
Co-authorships, Clinical Studies, and Reviews:
In Situ Forming Gelatin Hydrogels-Directed Angiogenic Differentiation and Activity of Patient-Derived Human Mesenchymal Stem Cells.
Lee Y, Balikov DA, Lee JB, Lee SH, Lee SH, Lee JH, Park KD, Sung HJ.
Int J Mol Sci. 2017 Aug 4;18(8). pii: E1705. doi: 10.3390/ijms18081705.
Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis.
Ford CA, Cassat JE.
Expert Rev Anti Infect Ther. 2017 Aug 24. doi: 10.1080/14787210.2017.1372192. [Epub ahead of print]
McDonough EM, Barrett CW, Parang B, Mittal MK, Smith JJ, Bradley AM, Choksi YA, Coburn LA, Short SP, Thompson JJ, Zhang B, Poindexter SV, Fischer MA, Chen X, Li J, Revetta FL, Naik R, Washington MK, Rosen MJ, Hiebert SW, Wilson KT, Williams CS.
JCI Insight. 2017 Aug 17;2(16). pii: 78210. doi: 10.1172/jci.insight.78210. [Epub ahead of print]
Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.
Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM.
Nat Genet. 2017 Aug 7. doi: 10.1038/ng.3929. [Epub ahead of print]
Prospective Cohort Study of Uterine Fibroids and Miscarriage Risk.
Hartmann KE, Velez Edwards DR, Savitz DA, Jonsson-Funk ML, Wu P, Sundermann AC, Baird DD.
Am J Epidemiol. 2017 Jun 7:1-9. doi: 10.1093/aje/kwx062. [Epub ahead of print]
Read more about this publication here and here.
Consensus statement on current and emerging methods for the diagnosis and evaluation of cerebrovascular disease.
Donahue MJ, Achten E, Cogswell PM, De Leeuw FE, Derdeyn CP, Dijkhuizen RM, Fan AP, Ghaznawi R, Heit JJ, Ikram MA, Jezzard P, Jordan LC, Jouvent E, Knutsson L, Leigh R, Liebeskind DS, Lin W, Okell TW, Qureshi AI, Stagg CJ, van Osch MJ, van Zijl PC, Watchmaker JM, Wintermark M, Wu O, Zaharchuk G, Zhou J, Hendrikse J.
J Cereb Blood Flow Metab. 2017 Jan 1:271678X17721830. doi: 10.1177/0271678X17721830. [Epub ahead of print]