Katherine N. Scott

Prognosis in Women With Myocardial Ischemia in the Absence of Obstructive Coronary Disease Results From the National Institutes of Health–National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Background—We previously reported that 20% of women with chest pain but without obstructive coronary artery disease (CAD) had stress-induced reduction in myocardial phosphocreatine–adenosine triphosphate ratio by phosphorus-31 nuclear magnetic resonance spectroscopy (abnormal MRS), consistent with myocardial ischemia. The prognostic implications of these findings are unknown. Methods and Results—Women referred for coronary angiography for suspected myocardial ischemia underwent MRS handgrip stress testing and follow-up evaluation. These included (1) n= 60 with no CAD/normal MRS, (2) n= 14 with no CAD/abnormal MRS, and (3) n= 352 a reference group with CAD. Cardiovascular events were death, myocardial infarction, heart failure, stroke, other vascular events, and hospitalization for unstable angina. Cumulative freedom from events at 3 years was 87%, 57%, and 52% for women with no CAD/normal MRS, no CAD/abnormal MRS, and CAD, respectively (P < 0.01). After adjusting for CAD and cardiac risk factors, a phosphocreatine–adenosine triphosphate ratio decrease of 1% increased the risk of a cardiovascular event by 4% (P = 0.02). The higher event rate in women with no CAD/abnormal MRS was primarily due to hospitalization for unstable angina, which is associated with repeat catheterization and higher healthcare costs. Conclusions—Among women without CAD, abnormal MRS consistent with myocardial ischemia predicted cardiovascular outcome, notably higher rates of anginal hospitalization, repeat catheterization, and greater treatment costs. Further evaluation into the underlying pathophysiology and possible treatment options for women with evidence of myocardial ischemia but without CAD is indicated.

NMR parameters of biologically important aromatic acids I. Benzoic acid and derivatives

Abstract Precise values of aromatic proton chemical shifts and coupling constants for phenol, anisole, and 22 hydroxy- and methoxy-substituted benzoic acids and methyl benzoates were obtained from the complete computer analysis of the spectra. The additivity of substituent effects on the aromatic and methyl proton chemical shifts is evaluated in detail in order to establish the reliability of the predicted chemical shifts. The importance of solvent effects on empirical chemical shift parameters is stressed. The coupling constants for mono- and disubstituted benzoic acids could be predicted from additivity. The nonadditivity of the methoxy-substituted methyl benzoate coupling constants is attributed to the steric interaction of the bulky methoxy and methyl ester groups.

Exploiting the Stimulated Echo in Nuclear Magnetic Resonance Imaging. I. Method

There is an adage that applies equally to all multipulse NMR experiments which states it is easier to induce spin ethos than not. Rather than ignore or suppress these additional ethos in NMR imaging experiments (I) we wish to communicate techniques which glean added information from them. In particular we exploit the unique properties of the stimulated echo as first identified by Hahn (2) and further quantified by Woessner (3). Although new to NMR imaging, stimulated ethos have been successfully applied by Tanner to the measurement of translational selfdiffusion coefficients (4), by Lausch and Spiess to study infrequent jumps of complex molecules (5, 6), and more recently to analyze slow rotational motions of molecular solids by Sullivan et al. (7). This communication will outline the methodology involved in the execution of stimulated echo NMR imaging. A subsequent communication (8) will present specific applications, and is henceforth referred to as Part II. Consider a spin system in thermal equilibrium with its surroundings subjected to the rf pulse and magnetic field gradient pulse experiment depicted in Fig. 1. We bring the net magnetization into the transverse plane with the transmission (TX) of a 7r/2 rf pulse. Unless stated to the contrary, the rf pulse is of frequency wp and width t,, such that t,, is small compared to Ti and T2, and excites the entire chemical shift frequency bandwidth equally. If, for example, the pulse has phase A equal to 0” (i.e., along the positive y direction), the transverse magnetization will initially be aligned with the positive x direction in the rotating frame. Free precession of all isochromats occurs during the time interval 7,. During this time span we apply pulsed magnetic field gradients as in the conventional Fourier imaging technique (9). The preparatory readout gradient is embodied in the effective x gradient (G,), whereas GY and G , are employed for phase encoding. Obviously z-direction discrimination could also be achieved with a selective 7r/2 rf pulse applied in the presence of G , (10). A second 7r/2 rf pulse is applied at the end of the 71 interval. Thus far the rf pulse sequence described is simply Hahn’s original spin echo experiment (2). Hence

Exploiting the stimulated echo in nuclear magnetic resonance imaging. II. Applications

Abstract Possible applications are presented of the recently reported technique of stimulated-echo nuclear magnetic resonance imaging. Exploiting stimulated echoes in NMR imaging involves the prudent use of the ability to store and retrieve information along the longitudinal direction, which is fundamental to the formation of the stimulated echo. T 1 multiecho imaging is presented, resulting from the extension of the basic stimulated-echo imaging sequence by additional π/2 rf pulses. It is shown that stimulated-echo imaging may result in the quantitative determination of T 1 values. By incorporating the stimulated echo into chemical-shift imaging techniques it is possible to suppress the shorter T 1 elements of a sample. This is in contrast with conventional spin-echo imaging, where the longer T 1 elements are suppressed. Additionally, a method of in vivo determination of molecular translational self-diffusion coefficients, which utilizes the stimulated echo to lessen the effect of T 2 relaxation, is proposed.

Spectrum simplification by broadband homonuclear decoupling

Abstract A method of spectrum simplification by broadband homonuclear decoupling is described and illustrated with the spectrum of dimethyl N-(phenylacetyl)-L-glutamate.

Evaluation of Skeletal Muscle Metabolic Responses Following Exercise Training in Patients with Intermittent Claudication

Objective: Factors responsible for the exercise intolerance occurring in patients with peripheral arterial occlusive disease (PAOD) manifesting intermittent claudication (IC) and contributing to the observed improvements in walking capacity after exercise training have not been elucidated. The authors characterized the resting and exercise responses of high-energy phosphate species in affected calf skeletal muscle as detected by phosphorus (P)-31 magnetic resonance spectroscopy (MRS) to determine whether metabolic derangements were present in patients with mild to moderate PAOD and IC and whether these abnormalities could be altered by training. Subjects: Thirteen patients evaluated for IC with resting ankle-brachial indices (ABIs) < 0.9 and positive exercise testing were enrolled in a supervised 10-week walking exercise program (IC training). Separate control groups were composed of (1) patients with PAOD and IC (IC control, n = 4) and (2) healthy, age-matched individuals (n = 4) without PAOD or IC who did not undergo exercise training. Outcome Measures: Resting ABIs and constant-load treadmill testing were performed prior to and following exercise training. ABIs, ankle pressure drop, and calf muscle bioenergetic response (P-31 MRS) of the most symptomatic limb were measured during inmagnet, lowand high-intensity calf exercise done before and after training. Results: Compared with healthy controls, patients with PAOD and IC before training had lower resting ABIs (0.66 ±0.11), larger ankle pressure drops (35 ±15%), shorter symptom-free walking distances during treadmill testing and significantly slower phosphocreatine recovery (Pcr t½) during in-magnet low-intensity (61 ±46 v. 36 ±40 sec, p=0.05) and high (119 ±93 v. 31 ±10 sec, p=0.003) exercise but had otherwise similar bioenergetic responses. Despite improved symptom-free walking distance (1,080 ±316 v. 498 ±367 ft, p < 0.001), patients with PAOD and IC exhibited no changes in resting ABI, ankle pressure drop or high-energy phosphate responses after training. Furthermore, no significant correlation was found between high-energy phosphate species and limb hemodynamics. Conclusions: The relatively subtle abnormalities in high-energy phosphate muscle metabolism present in patients with PAOD and IC may only partially account for their marked exercise intolerance and do not appear to contribute to the observed improvement in walking capacity after supervised training.

Automatic analysis of nuclear-magnetic-resonance-spectroscopy clinical research data

A major problem of P-31 nuclear magnetic spectroscopy (MRS) in vivo applications is that when large data sets are acquired, the time invested in data reduction and analysis with currently available technologies may totally overshadow the time required for data acquisition. An example is out MRS monitoring of exercise therapy for patients with peripheral vascular disease. In these, the spectral acquisition requires 90 minutes per patient study, whereas data analysis and reduction requires 6-8 hours. Our laboratory currently uses the proprietary software SA/GE developed by General Electric. However, other software packages have similar limitations. When data analysis takes this long, the researcher does not have the rapid feedback required to ascertain the quality of data acquired nor the result of the study. This highly undesirable even in a research environment, but becomes intolerable in the clinical setting. The purpose of this report is to outline progress towards the development of an automated method for eliminating the spectral analysis burden on the researcher working in the clinical setting.