Joseph J.H. Ackerman
Washington University School of Medicine
Biomedical Magnetic Resonance Laboratory
Campus Box 8227
4525 Scott Avenue
St. Louis, MO 63110
William Greenleaf Eliot Emeritus Professor of Chemistry
Professor of Radiology and Chemistry in Medicine
Magnetic Resonance of Intact Biological Systems: Ackerman and collaborators within the Biomedical MR Laboratory (BMRL) are focused on the development and application of magnetic resonance spectroscopy (MRS) and imaging (MRI) for study of intact, functioning biological systems representing both Animalia and Plantae Kingdoms. Cell/tissue function and structure are accessible via MR methods, advantages of which include: ● non-ionizing radiation (MR techniques are inherently non-invasive and non-destructive); ● simultaneous, multi-component metabolic analysis; and ● sensitivity to subtle changes in motion/displacement, magnetic susceptibility, and structure at the molecular, micro-, and mesocopic levels. Two projects serve to illustrate this theme.
Diffusion-Sensitive MR: The incoherent displacement motion of tissue water is hindered and restricted by various micro-structural barriers. Mammalian tissue water diffusion can be readily monitored by MR and has proven of great value in characterizing a variety of normal and pathologic states, providing a unique means to assess/quantify cancer progression and therapy, neurodegenerative diseases, and developmental neurobiology. Unfortunately, the manner in which the MR water diffusion signal encodes tissue microstructure and function remains poorly understood. Thus, elucidating the biophysical phenomena governing water diffusion in tissue systems is a critical area of MR research, and the BMRL is prominent in this arena. Ackerman and collaborators employ diffusion-sensitive MR methods with carefully chosen model systems ranging from cultured cells, to small animals (mice, rats), to humans, in concert with efforts to develop biophysical models that quantitatively describe the effects of various micro-structural barriers as reflected in the MR diffusion signal.
Radiation Necrosis: Radiation therapy is the most efficient treatment to cure or mitigate malignant brain tumors. However, approximately 20% of patients experience radiation necrosis six or more months following therapy and the presence of radiation necrosis complicates/masks the identification/diagnosis of recurrent tumor. MRI methods hold promise for quantitative assessment of radiation necrosis but development has been hampered by lack of a well-developed small-animal model of radiation necrosis in which specific focal regions of mouse brain are targeted, a sine qua non for such studies. Gamma Knife irradiation (~200 low-dose radiation beams directed to an isocenter) enables single-hemisphere mouse-brain irradiation. This provides a powerful platform for development and validation of quantitative radiation-necrosis assessment by MRI, a research program ongoing in the BMRL
- “Anti-VEGF Antibodies Mitigate the Development of Radiation Necrosis in Mouse Brain”, X. Jiang, J. A. Engelbach, L. Yuan, J. Cates, F. Gao, R. E. Drzymala, D. E. Hallahan, K. M. Rich, R. E. Schmidt, J. J. H. Ackerman, and J. R. Garbow, Clin. Can. Res., accepted (2014).
- “A GSK-3β Inhibitor Protects Against Radiation Necrosis in Mouse Brain”, X. Jiang, C. J. Perez-Torres, D. Thotala, J. A. Engelbach, L. Yuan, J. Cates, F. Gao, R. E. Drzymala, K. M. Rich, R. E. Schmidt, D. E. Hallahan, J. J. H. Ackerman, and J. R. Garbow, Int. J. Radiat. Oncol. Biol. Phys., accepted (2014).
- “Towards Distinguishing Recurrent Tumor from Radiation Necrosis: DWI and MTC in a Gamma Knife® Irradiated Mouse Glioma Model”, C. J. Perez-Torres, J. A. Engelbach, J. Cates, D. K. Thotala, K. M. Rich, R. E. Drzymala, J. J.H . Ackerman, and J. R. Garbow, Int. J. Radiat. Oncol. Biol. Phys., accepted (2014).
- “Diffusion Sensitive Magnetic Resonance Imaging of the Central Nervous System”, J. J. Neil and J. J. H. Ackerman, in Advances in Neurobiology, Vol 4, Neural Metabolism In Vivo, pages 65-78 (In-Young Choi and Rolf Gruetter, eds.), Springer, New York, (2012).
- "The Use of Ethylene Glycol to Evaluate Gradient Performance in Gradient-Intensive Diffusion MR Sequences", W. M. Spees, S.-K. Song, J. R. Garbow, J. J. Neil, and J. J.H. Ackerman, Magn. Reson. Med., 68: 319-324 (2012); PMCID: PMC3296827.
- "Semi-permeable Hollow Fiber Phantoms for Development and Validation of Perfusion-Sensitive MR Methods and Signal Models”, J. R. Anderson, J. J. H Ackerman, and J. R. Garbow, Concepts in Magn. Reson. Part B: Magn. Reson. Eng., 39B: 149-158 (2011).
- "Diffusion Effects on Longitudinal Relaxation in Poorly Mixed Compartments”, J. R. Anderson, Q. Ye, J. J. Neil, J. J. H Ackerman, and J. R. Garbow, J. Magn. Reson., 211:30-36 (2011); PMCID PMC3114270.
- “Imaging Primary Lung Cancers in Mice to Study Radiation Biology: in Regard to Kirsch et al. (Int. J. Radiat. Oncol. Biol. Phys. 2010; 76: 973-977)” J. R. Garbow, and J. J. H. Ackerman, Int. J. Radiat. Oncol. Biol. Phys., 79: 959 (2011).
- "Quantification and Compensation of Eddy-Current-Induced Magnetic Field Gradients", W. M. Spees, N. Buhl, P. Sun, J. J. H. Ackerman, J. J. Neil, and J. R. Garbow, J. Magn. Reson., 212:116-123 (2011); PMCID: PMC3163721.
- "Protein-Induced Water 1H MR Frequency Shifts: Contributions from Magnetic Susceptibility and Exchange" J. Luo, X. He, D. A. d'Avignon, J. J. H. Ackerman, and D. A. Yablonskiy, J. Magn. Reson., 202: 102-108 (2010); PMCID: PMC2818297.
- "The Use of MR-Detectable Reporter Molecules and Ions to Evaluate Diffusion in Normal and Ischemic Brain" J. J. H. Ackerman and J. J. Neil, NMR in Biomedicine 23: 725-733 (2010); PMCID: PMC3080095.
- "Biophysics of Diffusion in Cells”, J. J. H. Ackerman and J. J. Neil, in Diffusion MRI: Theory, Methods and Applications (D. Jones, ed.), Chapter 8, Pages 110-124, Oxford University Press, Oxford, 2010.
- "Magnetic Resonance Diffusion Characteristics of Histologically Defined Prostate Cancer in Humans", J. Xu, P. A. Humphrey, A. S. Kibel, A. Z. Snyder, V. R. Narra, J. J. H. Ackerman, and S.-K. Song, Magn. Reson. Med., 61: 842-850 (2009).
- “High Dynamic Range MRS [Bayesian] Time-Domain Signal Analysis”, G. L. Bretthorst, W. C. Hutton, J. R. Garbow, and J. J. H. Ackerman, Magn. Reson. Med., 62: 1026-1035 (2009); PMCID: PMC2930376.
- "Magnetization Transfer Induced Biexponential Longitudinal Relaxation", A.M. Prantner, G. L. Bretthorst, J. J. Neil, J. R. Garbow, and J. J. H. Ackerman, Magn. Reson. Med., 60: 555-563 (2008); PMCID: PMC2702166.
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