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.

RECENT REVIEWS

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.

OTHER APPOINTMENTS:

Affiliations:

International Society of Magnetic Resonance in Medicine

Publications:

1.        Bottomley PA, Pope JM, Cornell BA. "A proton magnetic resonance study of the motion of cage water molecules in the clathrate hydrate of Xenon".  Mol Phys 1976; 31: 1277-1281.

2.        Holland GN, Bottomley PA.  "A colour display technique for NMR imaging".  J Phys. E: Sci. Instrum. 1977; 10: 714-716.

3.        Andrew ER, Bottomley PA, Hinshaw WS, Holland GN, Moore WS, Simaroj C.  "NMR images by the multiple sensitive point method: Application to larger biological systems".  Phys Med Biol 1977; 22: 971-974.

4.        Holland GN, Bottomley PA, Hinshaw WS. "19F magnetic resonance imaging".  J Magn Reson 1977; 28: 133-136.

5.        Hinshaw WS, Bottomley PA, Holland GN.  "Radiographic thin section image of the human wrist by nuclear magnetic resonance".  Nature 1977; 270: 722-723.

6.        Bottomley PA, Hinshaw WS, Holland GN.  "A computer driven photoscanner for medical imaging".  Phys. Med. Biol. 1978; 23: 309-317.

7.        Hinshaw WS, Andrew ER, Bottomley PA, Holland GN, Moore WS, Worthington BS.  "Display of cross-sectional anatomy by nuclear magnetic resonance imaging".  Brit J Radiol 1978; 51: 273-280.

8.        Bottomley PA. "A technique for the measurement of tissue impedance from 1 to 100 MHz using a vector impedance meter".  J Phys E: Sci Instrum 1978; 11: 413-414.

9.        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.

10.      Hinshaw WS, Andrew ER, Bottomley PA, Holland GN, Moore WS, Worthington BS.  "Internal structural mapping by NMR Imaging".  Neuroradiol 1978; 16: 607-609.

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Contact Information:

Phone: 410.955.0366

FAX: ....410.614.1977

email: bottoml@mri.jhu.edu