Research Interests

The focus of our work is the development and evaluation of magnetic resonance (MR) techniques that will hopefully lead to an every-day clinical application of the modality to the heart, especially to ischemic heart disease.

• Phosphorus MR studies of myocardial energy metabolism

We have used spatially localized phosphorus MR spectroscopy (MRS) to measure noninvasively high-energy phosphate metabolites such as ATP (adenosine triphosphate) and phosphocreatine (PCr) in the heart. These metabolites are responsible for muscular contraction: their 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.

We need to extend the techniques to permit measurements in the posterior and inferior walls Work is underway to combine new MR detector technology with MR enhancement and image processing techniques to increase the signal-to-noise ratio (SNR), and thereby improve access of the technique to deeper regions in the heart.

• Proton MR studies of myocardial creatine

Creatine is an important metabolite produced with ATP from the dephosphorylation of PCr. The total creatine pool is represented in the proton MRS spectrum by the N-CH3 resonance at 3.0 ppm. Detection by proton MRS has the advantages of much higher SNR than detection of PCr by 31P MRS, owing to higher sensitivity and concentration. Currently we are studying the use of MRS measures of creatine as a possible index of viability of heart tissue following myocardial infarction.

Representative publication:

Bottomley PA, Weiss RG. Noninvasive magnetic resonance detection of reatine depletion in non-viable infarcted myocardium. The Lancet 1998;351;714- 18.

• Perfusion-sensitive MRI

The development of techniques in MRI which may provide enhanced sensitivity to the image intensity of myocardial perfusion based on MR relaxation effects, specifically T1, are underway. The hope is that during ischemic stress and/or infarction image contrast can be improved to permit direct visualization of jeopardized/infarcted myocardium. Theoretical work on the fundamental nature of MR relaxation phenomena, the prominent source of MR image contrast, is also a continuing interest.

Other Appointments:

Affiliations:

International Society of Magnetic Resonance in Medicine

Publications:

•  Bottomley PA . Spatial localization in NMR spectroscopy in vivo. Annal NY Acad Sci 1987; 508: 333-348.

•  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. Roemer, PB. Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance. Magn Res Med 1990; 14: 425-434.

•  Weiss R,Bottomley P,Hardy C,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.

•  Bottomley PA, Weiss RG, Hardy CJ, Baumgartner WA. Myocardial high-energy phosphate metabolism and allograft rejection in patients with heart transplants. Radiology 1991; 181: 67-75.

•  Hardy CJ, Weiss RG, Bottomley PA, Gerstenblith G. Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy. Am Heart J 1991; 122: 795-801.

•  Bottomley PA, Ouwerkerk R. Fast sensitive T1 measurement in vivo with low angle adiabatic pulses: the dual-angle method. J Magn Reson 1994; 104 B:159-167.

•  Bottomley P.NMR spectroscopy of the human heart: the status and the challenges.Radiol 1994;191:593-612.

•  Dumoulin CL, Bottomley PA, Souza SP (1994). Magnetic resonance active invasive devices for the generation of selective MR angiograms. RD 21,822. US patent 5,447,156 ( Sept 5, 1995 ).

•  Bottomley PA, Atalar E, Weiss RG. Human cardiac high-energy phosphate metabolite concentrations by 1D-resolved NMR spectroscopy. Magn Reson Med 35; 664-670 (1996).

•  Atalar E, Bottomley PA, Ocali O, Correia LCL, Kelemen MD, Lima JAC, Zerhouni EA. High resolution intravascular MRI and MRS using a catheter receiver coil. Magn Reson Med 1996; 36: 596-605.

•  Atalar E, Bottomley PA, Zerhouni E. Method of internal magnetic resonance imaging and spectroscopic analysis and associated apparatus DM-9911. US patent 5,699,801 ( Dec 23, 1997 ).

•  Bottomley PA, Lugo Olivieri, CH, Giaquinto R. What is the optimum phased-array coil design for cardiac and torso magnetic resonance? Magn Reson Med 1997; 37: 591-599.

•  Bottomley PA, Lee YH, Weiss RG. Total creatine in muscle: imaging and quantification with proton MR spectroscopy. Radiology 1997; 204: 403-410.

•  Conway MA , Bottomley PA, Ouwerkerk R, Radda GK, Rajagopalan B. Mitral Regurgitation: Impaired Systolic Function, Eccentric Hypertrophy, and Increased Severity Are Linked to Lower Phosphocreatine/ATP Ratios in Humans. Circulation 1998; 97: 1716-1723.

•  Bottomley PA, Weiss RG. Noninvasive magnetic resonance detection of creatine depletion in non-viable infarcted myocardium. The Lancet 1998; 351: 714-718.

•  Lee RF,Giaquinto R,Constantinides, Souza S,Weiss RG,Bottomley PA. A broadband phased-array system for direct phosphorus and sodium metabolic MRI on a clinical scanner. Magn Reson Med 2000; 43:269-277.

•  Constantinides C, Gillen JS, Boada FE, Pomper MG, Bottomley, PA. Sodium MRI and quantification in human skeletal muscle: potential applications in exercise and disease. Radiology 2000; 216: 559-568.

•  Bottomley PA. Method and apparatus for determining or imaging longitudinal spin lattice relaxation time or producing images which substantially reflect longitudinal spin lattice time contrast.US Patent 6,064,203; 2000.

•  Ouwerkerk R, Bottomley PA. On neglecting chemical exchange effects when correcting in vivo 31P MRS for partial saturation. J Magn Reson 2001; 148: 425-435.

•  Bottomley PA, Weiss RG. Noninvasive localized magnetic resonance quantification of creatine kinase metabolites in normal and infarcted canine myocardium. Radiology 2001; 219: 411-418.

•  Lee RF, Westgate CR, Weiss RG, Newman D, Bottomley PA. The planar strip array (PSA) for parallel spatial encoded MRI. Magn Reson Med 2001; 45: 673-683.

•  Bottomley PA, Ouwerkerk R, Lee RF, Weiss RG. Four angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo. Magn Reson Med 2002; 47: 850-863.

•  Ouwerkerk R, Bleich KB, Gillen JS, Pomper MG, Bottomley PA. Tissue Sodium Concentration In Human Brain Tumors as Measured with 23Na MR Imaging. Radiology 2003; 227:529-537.

•  Gao F, Bottomley PA, Arnold C, Weiss RG. The effect of orientation on ... MRI 2003; 21: 561-566.

•  Lee RF, Hardy CJ, Sodickson DK, Bottomley PA. Lumped-element planar strip array (LPSA) for parallel MRI. Magn Reson Med. 2004 Jan;51(1):172-83.

•  Jacobs MA, Barker PB, Bottomley PA, Bhujwalla Z, Bluemke DA. Proton magnetic resonance spectroscopic imaging of human breast cancer: a preliminary study. J Magn Reson Imaging. 2004 Jan;19(1):68-75

•  McCaffrey RJ, Cousins JP, Westervelt HJ, Martynowicz M, Remick SC, Szebenyi S, Wagle WA, Bottomley PA, Hardy CJ, Haase RF. Practice effects with the NIMH AIDS abbreviated neuropsychological battery. Arch Clin Neuropsychol. 1995 May;10(3):241-50.

•  Gao F, Bottomley PA, Arnold C, Weiss RG. The effect of orientation on quantification of muscle creatine by 1H MR spectroscopy. Magn Reson Imaging. 2003 Jun;21(5):561-6.

•  Jacobs MA, Barker PB, Bottomley PA, Bhujwalla Z, Bluemke DA. Proton magnetic resonance spectroscopic imaging of human breast cancer: a preliminary study. J Magn Reson Imaging. 2004 Jan;19(1):68-75

 

 

 

 

 

 

 

 

 

 

Contact Information:

Phone: 410.955.0366

FAX: ....410.614.1977

email: bottoml@mri.jhu.edu