Phil Lee, Ph.D.

Associate Professor
Director of MR Technology
University of Minnesota, 2000

Research Focus

Neurophysiology and neuroimaging - Characterization and understanding of functional and physiological processes of the brain in vivo in health and disease using advanced non-invasive neuroimaging techniques.

Research Overview

Specific research interests include the development of novel magnetic resonance imaging (MRI) techniques and the identification of biomarkers to assess the integrity of structural, functional, physiological aspects of the brain in vivo at the cellular and molecular level. The research goals of our team are 1) to understand key pathologic mechanisms underlying disease activity, clinical status and disease progression in neurological disorders including Alzheimer disease and multiple sclerosis in the living brain, 2) to develop imaging methods to detect the pathologic changes at an early stage of the disease, 3) to guide the development of new targeted therapies and intervention strategies, and 4) to offer novel possibilities for directly monitoring the impact of these emergent treatment options through new quantitative, non-invasive biomarkers.

Research Highlights

Pre-clinical research – Early axonal transport deficits in Alzheimer Disease:
Neuronal cell viability critically depends on effective and timely function of the axonal transport system. Axonal transport is the process by which intracellular cargoes including neurotransmitters, protein and organelles are trafficked through axons to the nerve terminals. Axonal transport deficits have been linked to the pathogenic processes of neurodegenerative diseases such as Alzheimer disease in which axonal swellings and degeneration are prevalent. The development of non-invasive neuroimaging techniques to quantitatively assess axonal transport deficits in the brain in vivo would be enormously valuable to visualize early and subtle changes in the disease, to monitor the disease progression and to quantify the effect of drug intervention. A triple transgenic mouse model of Alzheimer disease (3xTg-AD) closely models neuropathology of Alzheimer disease in humans. Our team investigated age-dependent alterations in axonal transport rates in the olfactory system of 3xTg-AD mice in a longitudinal assessment, using a fast multi-slice T1 mapping technique with manganese-enhanced MRI. Our data suggest that the impairment in axonal transport is a very early event in Alzheimer disease pathology in these mice, preceding both deposition of Aβ plaques and formation of Tau fibrils, and that these deficits persist at older ages.

Early axonal transport deficits in Alzheimer research images

Clinical Research – Assessing microstructural changes in the brain of patients with multiple sclerosis:
Multiple sclerosis has been known as a white matter disease in the human brain. However, increasing evidence suggests the presence of gray matter pathology, which has been suggested to be closely associated with disease status and cognitive deficits. A new generation of MRI techniques allow us to explore new possibilities to visualize such pathology in living humans. A new emerging MRI technique, diffusional kurtosis imaging (DKI), can characterize microstructural organization at the cellular level through evaluation of both Gaussian and non-Gaussian properties of water diffusion. We studied over 50 patients with multiple sclerosis to measure subtle microstructural changes among major subtypes of the disease at 3 Tesla using DKI, and investigate association between DKI parameters and cognitive function such as memory and executive function and processing speed. Our data showed that diffusion parameters were sensitive to distinguish the microstructural differences among the subtypes of multiple sclerosis and these parameters were correlated with the disease duration and the clinical disease severity scale of multiple sclerosis, Expanded Disability Status Scale (EDSS), as well as information processing speed and executive planning. We found that various diffusion parameters could indicate different pathologic features of multiple sclerosis in a region-specific manner and show promise in serving as sensitive biomarkers of the pathophysiology.

Selected Publications

  • J. Kim, I.-Y. Choi, Y. Dong, W.-T. Wang, W.M. Brooks, C.P. Weiner, P. Lee, “Chronic fetal hypoxia affects axonal maturation in guinea pigs during development: a longitudinal Diffusion Tensor Imaging and T2 mapping study”, J Magn Reson Imaging 42(3):658-65 (2015) PMID: 25504885
  • I.-Y. Choi, P. Lee, D.R. Denney, K. Spaeth, O. Nast, L. Ptomey, A.K.  Roth, J.A. Lierman, D.K. Sullivan. Dairy intake is associated with brain glutathione concentrations in older adults. Am J Clin Nutr 101(2):287-93 (2015) PMID: 25646325
  • I.-Y. Choi, P. Lee, D. Hui, X. Wang, W. M. Brooks, E. K. Michaelis, Cerebral metabolism changes during aging in the hippocampus and striatum of Glud1 (Glutamate Dehydrogenase 1) transgenic mice, Neurochem Res 39(3):446-55 (2014) PMID: 24442550
  • S.G. Kim, N. Harel, T. Jin, T. Kim, P. Lee, F. Zhao, Cerebral blood volume MRI with intravascular superparamagentic iron oxide nanoparticles, NMR in Biomed 26(8):949-62 (2013) PMID: 23208650
  • J.E. Johnson, P. Lee, T.E. McIff, E.B. Toby, K.J. Fischer, Scapholunate ligament injury adversely alters in vivo wrist joint mechanics: an MRI-based modeling study, J Orthop Res. 31(9):1455-60 (2013) PMID: 23575966
  • Y. Ma, G.G. Sullivan, E. Schrick, I.-Y. Choi, Z. He, J.A. Lierman, P. Lee, J.A. Drisko, Q. Chen, “A convenient method for measuring blood ascorbate concentrations in patients receiving high-dose intravenous ascorbate” J Am Coll Nutr 32(3):187-193 (2013) PMID: 23885992
  • I.-Y. Choi, P. Lee, Doubly selective multiple quantum chemical shift imaging and T1 relaxation time measurement of glutathione (GSH) in the human brain in vivo, NMR biomed 26(1):28-34 (2012) PMID: 22730142
  • P. Lee, J. Kim, R. Williams, R. Sandhir, E. Gregory, W.M. Brooks, N.E. Berman, Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice, Exp Neurol 234(1):50-61 (2012) PMID: 22201549.
  • W.-T. Wang, P. Lee, I.V. Smirnova, I.-Y Choi, Effects of acute- and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo 1H MR spectroscopy at 9.4 T, J Neurochem 121(3):407-417 (2012) PMID: 22353009
  • C.M. Cirstea, R. Nudo, C.S. Craciunas, A.E. Popescu, I.-Y. Choi, P. Lee, H.-W. Yeh, C. Savage, W.M. Brooks, Neuronal-glial alterations in non-primary motor areas in chronic subcortical stroke, Brain Res 1463:75-84 (2012) PMID: 22575560
  • I.-Y. Choi, P. Lee, Doubly selective multiple quantum chemical shift imaging and T1 relaxation time measurement of glutathione (GSH) in the human brain in vivo, NMR biomed 26(1):28-34 (2012) PMID: 22730142
  • C.M. Cirstea, W.M. Brooks, C.S. Craciunas, A.E. Popescu, I.-Y. Choi, P. Lee, A. Bani-Ahmed, H. Yeh, C.R. Savage, L.G. Cohen, R. Nudo, Primary motor cortex in stroke – a functional MRI-guided proton magnetic resonance spectroscopic study.  Stroke 42(4):1004-9 (2011) PMID: 21330627
  • J. Kim, I.-Y. Choi, M. L. Michaelis, P. Lee, Quantitative in vivo measurement of early axonal transport deficits in a triple transgenic mouse model of Alzheimer’s disease using manganese enhanced MRI. NeuroImage 56(3):1286-92 (2011) PMID: 21338698
  • I.-Y. Choi, S.-P. Lee, D.R. Denney, S.G. Lynch, Lower levels of glutathione in the brains of secondary progressive multiple sclerosis patients measured by 1H magnetic resonance chemical shift imaging at 3 T, Mult Scler 17(3): 289-296 (2011) PMID: 20921235
  • M.H. Boudrias, S.-P. Lee, S. Svojanovsky, and P.D. Cheney, Forelimb muscle representations and output properties of the motor areas in the mesial wall of rhesus macaques, Cereb Cortex 20(3):704-19 (2010) PMID: 19633176
  • J. H. Jensen, R. Chandra, A. Ramani, H. Lu, G. Johnson, S.-P. Lee, K. Kaczynski, and J. A. Helpern, Magnetic field correlation imaging, Magn Reson Med 55(6):1350-61 (2006) PMID: 16700026
  • I.-Y. Choi, S.-P. Lee, H. Merkle and J. Shen, In vivo detection of gray and white matter differences in GABA concentration in the human brain, NeuroImage 33(1):85-93 (2006) PMID: 16884929
  • S.-P. Lee, M. F. Falangola, K. Duff, R. A. Nixon, J. A. Helpern,  Visualization of ß-Amyloid plaques in a transgenic mouse model of Alzheimer’s disease using MR Microscopy without contrast reagents, Magn Reson Med 52: 538-544 (2004) PMID: 15334572
  • I.-Y. Choi, S.-P. Lee, H. Merkle and J. Shen, A single shot, two-echo method for simultaneous detection of multiple quantum filtered GABA and single quantum creatine in the human brain in vivo, Magn Reson Med 51: 1115-1121 (2004) PMID: 15170830
  • N. Harel, S.-P. Lee, T. Nagaoka, D.-S. Kim, S.-G. Kim, Origin of negative blood oxygenation level-dependent fMRI signals, J Cereb Blood Flow Metab 22: 908-917 (2002) PMID: 12172376
  • S.-P. Lee, A. C. Silva, and S.-G. Kim, Comparison of diffusion-weighted CBF and spin-echo BOLD fMRI at 9.4 T, Magn Reson Med 47:735-741 (2002) PMID: 11948735
  • S.-P. Lee, T.Q. Duong, C. Iadecola, and S.-G. Kim, Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: Implications for BOLD fMRI, Magn Reson Med 45: 791-800 (2001) PMID: 11323805
  • I.-Y. Choi, S.-P. Lee, S.-G. Kim, R. Gruetter, In vivo measurements of brain glucose transport using a reversible Michaelis-Menten model and comparison with cerebral blood flow changes during hypoglycemia, J Cereb Blood Flow Metab 21:653-663 (2001) PMID: 11488534
  • T.Q. Duong, A.C. Silva, S.-P. Lee, S.-G. Kim, Functional MRI of calcium-dependent synaptic activity: Cross correlation with CBF and BOLD measurements, Magn Reson Med 43: 383-392 (2000) PMID: 10725881
  • A.C. Silva, S.-P. Lee, G. Yang, C. Iadecola, S.-G. Kim, Simultaneous blood oxygenation level-dependent and cerebral blood flow functional magnetic resonance imaging during forepaw stimulation in the rat, J Cereb Blood Flow Metab 19: 871-879 (1999) PMID: 10458594
  • S.-P. Lee, A.C. Silva, K. Ugurbil, and S.-G. Kirn, Diffusion-weighted spin-echo fMRI at 9.4 T: microvascular/tissue contribution to BOLD signal changes, Magn Reson Med 42: 919-928 (1999) PMID: 10542351
Last modified: Aug 28, 2015

Phil Lee, PhD


Phil Lee, Ph.D.
Associate Professor
Director of MR Technology

Hoglund Brain Imaging Center
3901 Rainbow Blvd, Mail Stop 1052
University of Kansas Medical Center
Kansas City, KS 66160

P: (913) 588-0454
F: (913) 588-9071