britton chance: the development of in vivo mrs mitchell schnall md, phd

Britton Chance: The Development of In Vivo MRS

Mitchell Schnall MD, PhD

Metabolism as a basis for understanding and curing disease

Warm Ischemia4 degrees C

75 second spectrum

Exercising in the NMR magnet

The Transfer function: “Furthermore, the slope and extentof the linear portion of Fig. 4 are pivotal in the identification of normal and pathological functions of the limb.”

Figure 4

Assuming ADP control and Michaelis-Menten kinetics

assuming a constant pH of 7.1, a temperature of 370C, a 1.0-mM magnesium concentration, and a 5-mM ATP concentration giving Kobs, = 132 (1) and Km ADP = 20 AM (19, 24).

Vmax of 52 J/min and a Km of 0.65 ± 0.06.

PFK

Recovery kinetics as a Biomarker

PFK deficient PVD patient

Vitamin K3

Vitamin C

Detecting Treatment Response

0 5 10

Min

Normal Subject Patient prior to (A) and after (B) therapy

1985

BC’s Contribution to MRS• Established feasibility to real time measurement of metabolites in perfused

organs, intact animal models, and humans• Developed a mechanistic approach to interpretation of spectral data for the

purpose of clinical diagnostics• Developed a strategy of using MRS as a pharmaco-dynamic marker of

treatment effect• Established the role of PME (choline in the proton spectrum) as an important

marker of malignancy• Inspired the development of methodology to support further application of

MRS– Surface coils– Chemical shift imaging– Rotating frame imaging– Multinuclear spectroscopy– Hadamard spectroscopy– NMR pulse design methodology– Multimodality Optical-MR spectroscopy

Brit’s own acknowledgements