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Paul Bottomley, PhD

 

 


 

Paul A. Bottomley, Ph.D.
Director, Division of MR Research

RESEARCH INTERESTS

The application of nuclear magnetic resonance (NMR) techniques to biophysical, biological, and medical problems.  Theoretical, experimental, and technical development of NMR imaging (MRI); the development of methods for spatially localized spectroscopy (MRS); the measurement of relaxation times, diffusion constants, metabolite concentrations, kinetic reaction rates, energy supply and work in biological tissues using NMR.  The application of these technologies to the noninvasive study of human disease, especially heart disease. 

Measurements of energy metabolites and metabolic fluxes with phosphorus (31P) and proton (1H) MRS in patients with ischemia, infarction and heart failure.  Sodium (23Na) MRI in patients with ischemic disease, and with cancer.  Stress testing for ischemia using 31P MRS.  MRI detector coil design, phased-array detector coils including new strip detectors.  The development of new intravascular and internal MRI coils for imaging vascular and endothelial disease, and MRI-guided therapy delivery.  High-speed cardiovascular NMR imaging.  Molecular imaging.  New biomedical imaging modalities.

ACTIVE PROJECTS 

• Phosphorus MR studies of myocardial energy metabolism in human heart

We have used spatially localized phosphorus MR spectroscopy (MRS) to noninvasively measure high-energy phosphate metabolites such as ATP (adenosine triphosphate) and phosphocreatine (PCr) in the heart. The PCr/ATP ratio can change during stress-induced ischemia, and a protocol for stress-testing in the MR system has been developed which can detect the changes noninvasively in the anterior wall.

PCr is the heart’s primary energy reserve and is believed to play a role in shuttling cellular energy between sites of energy creation (mitochondria) and sites of energy utilization (eg, the myofibrils), via the creatine kinase (CK) reaction.  Because the forward CK reaction rate for producing ATP energy from PCr is many times the resting rate of ATP production from oxidative phosphorylation, the CK reaction could serve as a temporal energy buffer during times of stress and peak energy demand, for example, during cardiac contraction.

We have developed methods for noninvasively measuring the CK ATP energy supply–the CK flux–and used it to measure the CK ATP energy supply in the healthy heart at rest and exercise, in human myocardial infarction, and in human heart failure. Measurements in heart failure show reduction in ATP supply to a level that could contribute to an energy supply/demand imbalance during periods of increased demand.

• Interventional MRI technology

Advances in magnetic resonance imaging (MRI) technology can directly benefit diagnosis and intervention for the very broad range of research and clinical applications that MRI serves.  We have developed and optimized tiny MRI detector technology for fields of 3T and higher, demonstrating that the signal-to-noise ratio (SNR) increases quadratically with field strength and with the development of safety testing protocols, that such devices can be operated safely at higher field strength.
 
Ongoing work includes the development of an RF dosimeter that can measure incident specific absorption rates applied during MRI independent of the scanner, and the development of MRI-safe internal detectors for higher field use, that can translate the benefits of higher SNR to high resolution (≤100µm) and/or high speed local MRI.  One outcome is the development of an “MRI endoscope” that can provide real time and/or high resolution views of vessel anatomy from a frame-of-reference that is intrinsically locked to the device at the end of the probe.  Another is the development of a radiometric approach to detect any local heating associated with the device.

REVIEWS

Bottomley PA. MRS Studies of Creatine Kinase Metabolism in Human Heart. eMagRes, 2016, Vol 5: 1183–1202. DOI 10.1002/9780470034590.emrstm1488.

Bottomley PA. Sodium MRI in Man: Technique and Findings. eMagRes, 2012, Vol 1: 353–366. DOI 10.1002/9780470034590.emrstm1252.

Bottomley PA. NMR Spectroscopy of the Human Heart. In: Encyclopedia of Magnetic Resonance, eds R. K. Harris and R. E. Wasylishen, John Wiley: Chichester. DOI: 10.1002/9780470034590.emrstm0345.pub2. Published 15th September 2009.

Bottomley PA. State of the art. Human in vivo NMR spectroscopy in diagnostic medicine: clinical tool or research probe? Radiology 1989; 170: 1-15

Bottomley PA, Hardy CJ, Argersinger RE, Allen-Moore G. A review of 1H NMR relaxation in pathology: are T1 and T2 diagnostic? Med Phys 1987; 14: 1-37.

Bottomley PA, Foster TH, Argersinger RE, Pfeifer LM. A review of normal tissue hydrogen NMR relaxation times and relaxation mechanisms: dependence on tissue type, NMR frequency, temperature, species, excision, and age. Med Phys 1984; 11: 425-448.

BOOK

Bottomley PA, Griffiths JR. “HANDBOOK OF MAGNETIC RESONANCE SPECTROSCOPY IN VIVO. MRS Theory, Practice and Applications”. John Wiley & Sons Chichester, UK. 2016; ISBN: 978-1-118-99766-6; 1193 pages.

OTHER APPOINTMENTS:

Affiliations:

International Society of Magnetic Resonance in Medicine

Key Papers:

  1. Hinshaw WS, Bottomley PA, Holland GN. Radiographic thin section image of the human wrist by nuclear magnetic resonance. Nature 1977; 270: 722-723.
  2. Bottomley PA, Andrew ER. RF magnetic field penetration, phase-shift and power dissipation in biological tissue: Implications for NMR imaging. Phys Med Biol 1978; 23: 630-643.
  3. Nunnally RL, Bottomley PA. Assessment of pharmacological treatment of myocardial infarction by phosphorous-31 NMR with surface coils. Science 1981; 211: 177-180.
  4. Edelstein WA, Bottomley PA, Hart HR, Smith LS. Signal, noise and contrast in NMR imaging.  J Comp Assist Tomogr 1983; 7: 391-401.
  5. Bottomley PA, Hart HR, Edelstein, Schenck JF, Smith LS, Leue WM, Mueller OM, Redington RW.  NMR imaging/spectroscopy system to study both anatomy and metobolism. Lancet 1983; ii (322), 273-274.
  6. Bottomley PA, TH Foster, WM Leue. Chemical imaging of the brain by NMR. Lancet 1984; I (323): 1120.
  7. Bottomley PA, Hart HR, Edelstein WA, Schenck JF, Smith LS, Leue WM, Mueller OM, Redington RW. Anatomy and metabolism of the normal human brain studied by magnetic resonance at at 1.5 Tesla. Radiol 1984; 150, 441-446.
  8. Bottomley PA, Foster TH, Leue WM. In vivo nuclear magnetic resonance (NMR) chemical shift imaging by selective irradiation. Proc Natl Acad Sci 1984: 81: 6856-6860.
  9. Edelstein WA, Schenck JF, Hart HR, Hardy CJ, Foster TH, Bottomley PA. Surface coil magnetic resonance imaging. JAMA (J Am Med Assoc) 1985; 253: 828.
  10. Bottomley PA, Edelstein WA, Foster TH, Adams WA. Invivo solvent suppressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism?  Proc Natl Acad Sci USA 1985; 82: 2148-2152.
  11. Bottomley PA. Non-invasive study of high-energy phosphate metabolism in the human heart by depth resolved 31P NMR spectroscopy. Science 1985; 229: 769-772.
  12. Bottomley PA, Rogers HH, Foster TH. Nuclear magnetic resonance imaging shows water distribution and transport in plant root systems in situ. Proc Natl Acad Sci USA 1986; 83: 87-89.
  13. Bottomley PA. Spatial localization in NMR spectroscopy in vivo.   Annal NY Acad Sci 1987; 508: 333-348.
  14. Weiss RG, Bottomley PA, Hardy CJ, Gerstenblith G. Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease. N Engl J Med .1990; 323: 1593-1600.
  15. Bottomley PA, Weiss RG. Noninvasive MRS detection of localized creatine depletion in non-viable, infarcted myocardium. Lancet 1998; 351: 714-718.
  16. Weiss RG*, Gerstenblith G, Bottomley PA*. ATP Flux through Creatine Kinase in the Normal, Stressed, and Failing Human Heart.   Proc Natl Acad Sci USA 2005; 102: 808-813. 165.
  17. Bottomley PA, Wu KC, Gerstenblith G, Schulman SP, Steinberg A, Weiss RG.  Reduced myocardial creatine kinase flux in human myocardial infarction: An in vivo phosphorus magnetic resonance spectroscopy study. Circulation 2009; 119: 1918-24.
  18. Sathyanarayana S, Bottomley PA. MRI endoscopy using intrinsically localized probes. Med Phys 2009; 36: 908-919.
  19. Hirsch GA*, Bottomley PA*, Gerstenblith G, Weiss RG.  Allopurinol Acutely Increases ATP Energy Delivery in Failing Human Hearts. J Am Coll Cardiol 2012; 59: 802-808.
  20. Bottomley PA*, Panjrath GS*, Lai S, Hirsch GA, Wu K, Najjar SS, Steinberg A, Gerstenblith G Weiss RG. Metabolic Rates of ATP Transfer Through Creatine Kinase (CK flux) Predict Clinical Heart Failure Events and Death.  Science Transl Med 2013; 5: 215re3, pp1-8.

click here to see CV and the entire publication list

 

 

Contact Information:

Phone: 410.955.0366
FAX: ....410.614.1977
email: bottoml@mri.jhu.edu

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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