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Biomedical subjects

P M Robitaille

Publications and source records attributed to P M Robitaille.

At least 55 records · Page 3Linked to original sources
PubMed1993

Muscle metabolism during exercise in young and older untrained and endurance-trained men.

To examine effects of aging and endurance training on human muscle metabolism during exercise, 31P magnetic resonance spectroscopy was used to study the metabolic response to exercise in young (21-33 yr) and older (58-68 yr) untrained and endurance-trained men (n = 6/group). Subjects performed graded plantar flexion exercise with the right leg, with metabolic responses measured using a 31P surface coil placed over the lateral head of the gastrocnemius muscle. Muscle biopsy samples were also obtained for determination of citrate synthase activity. Rate of increase in P(i)-to-phosphocreatine ratio with increasing power output was greater (P < 0.01) in older untrained [0.058 +/- 0.022 (SD) W-1] and trained men (0.042 +/- 0.010 W-1) than in young untrained (0.038 +/- 0.017 W-1) and trained men (0.024 +/- 0.010 W-1). Plantar flexor muscle cross-sectional area and volume (determined using 1H magnetic resonance imaging) were 11-12% (P < 0.05) and 16-18% (P < 0.01) smaller, respectively, in older men. When corrected for this difference in muscle mass, age-related differences in metabolic response to exercise were reduced by approximately 50% but remained significant (P < 0.05). Citrate synthase activity was approximately 20% lower (P < 0.001) in older untrained and trained men than in corresponding young groups and was inversely related to P(i)-phosphocreatine slope (r = -0.63, P < 0.001). Age-related reductions in exercise capacity were associated with an altered muscle metabolic response to exercise, which appeared to be due to smaller muscle mass and lower muscle respiratory capacity of older subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

New calcium-sensitive ligand for nuclear magnetic resonance spectroscopy.

Fluorinated calcium-sensitive indicators such as 5,5'-difluoro-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (difluoro-BAPTA) will often be less sensitive under in vivo conditions than gyromagnetic ratio considerations alone would have predicted. This is due to the very broad line widths displayed by these molecules within the living cell. In order to provide a spectroscopic alternative to these molecules, we have synthesized 13C-enriched 1-(2-aminophenoxy)-2-(2-aminoethoxy)ethane-N,N,N',N'-tetraac etic acid or AATA. The rationale for the design of this molecule was the increased signal to noise ratio available by selective detection of 13C-attached protons in AATA using proton-observe carbon-edited spectroscopy or multiple-quantum coherence. AATA has the advantage of increased number of detectable nuclei and narrow line widths. As such, it should provide a 6-10-fold improvement in the signal to noise ratio over existing fluorinated indicators. As a hybrid between EGTA and BAPTA, AATA should display intermediate pKa's, exchange rates, and KD values. We have measured pKa values of 5.94 +/- 0.05 and 9.03 +/- 0.05 for AATA. KD values of 350 +/- 80 nM and 6.6 +/- 2.0 mM were obtained for the AATA-Ca2+ and AATA-Mg2+ interactions, respectively, at 37 degrees C in 0.1 M KCl. As such, this new ligand displays the expected selectivity for Ca2+ over Mg2+. This new approach to detection of intracellular probes with NMR can be readily extended to other probes for intracellular ions, pH, and membrane potential. In addition, the move toward carbon-selected proton spectroscopy should also permit more flexibility in synthetic approaches since the strong electronegativity of fluorine often hampers synthetic design.

Calcium↗
PubMed1992

Improved cardiac gating and ventilation timing in animal experiments.

In this work we present an improved solution for cardiac gating and ventilation timing in in vivo spectroscopic and imaging experiments. This approach makes use of a pulse conditioner to extract primary timing signals from noisy and fluctuating input signals. A timing controller is then used to set all additional timing outputs. Full feedback control is utilized in this timing controller to optimize both magnetic resonance and respiratory timing. Feedback control also helps ensure that timing errors will not occur during acquisition.

Animals↗
PubMed1990

Measurement of ATP synthesis rates by 31P-NMR spectroscopy in the intact myocardium in vivo.

The ability to measure ATP synthesis rates using 31P-NMR spectroscopy is demonstrated in the normal, ischemic, and postischemic myocardium in vivo. Cardiopulmonary bypass (CBP) was employed to induce 20 min of global myocardial ischemia, and to conduct magnetization transfer measurements during the ischemic episode and following reperfusion and return to normal circulation. For the first few minutes of ischemia, transfer of magnetization from ATP gamma to Pi was extensive and the resultant fractional reduction (delta M/M0) in the Pi resonance intensity reached approximately 100%. Subsequent to reperfusion and stabilization off CPB and on normal circulation, both the fractional reduction and the spin-lattice relaxation time, T1*, of the Pi resonance were determined when ATP gamma spins were saturated. Under these conditions, the unidirectional ATP synthesis rate was 0.41 +/- 0.09 (SEM, N = 4) mumol/s/g wet wt. The data suggest that in the canine myocardium in vivo, glycolytic enzymes mediate a very rapid exchange between Pi and ATP gamma-phosphates during early phases of ischemia; in the postischemic reperfused myocardium, however, the glycolytic contribution to the unidirectional Pi----ATP rate measured by NMR in vivo is relatively small compared to that observed in glucose-perfused, postischemic rat hearts.

Adenosine Triphosphate↗
PubMed1990

Transmural high energy phosphate distribution and response to alterations in workload in the normal canine myocardium as studied with spatially localized 31P NMR spectroscopy.

Spatially localized phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been applied to the study of the normal canine myocardium to measure the relative content of high energy phosphates across the left ventricular wall. Transmural NMR data were acquired in five voxels spanning the wall of the left ventricle using the FLAX-ISIS technique. The validity of the FLAX-ISIS approach in acquiring localized spectra for transmural studies and in providing quantitative information from the localized spectra was examined rigorously by studies involving phantoms, intact rats, and the canine myocardium in vivo. The results indicated that (1) this technique yields spatially resolved spectra with partial overlap between adjacent voxels and virtually no overlap between every other voxel; (2) in the canine heart, signals from subepicardium, midwall, and subendocardium can be detected separately without cross contamination; and (3) relative metabolite contents within a voxel and among voxels can be quantitated. Transmural 31P NMR spectra were acquired with cardiac gating on 29 separate animals either at early systole or late diastole, and at three different workloads with the heart rate peak systolic pressure product (RPP) increasing from 6000 mmHg/min to 35,000 mmHg/min. The data revealed that in the normal canine myocardium, the creatine phosphate (CP) content and the CP/ATP ratio was significantly lower in the subendocardium than in the subepicardium. ATP levels were transmurally constant. Both the CP content and the CP/ATP ratio measured for each voxel remained unaltered in relation to either the phase of the cardiac cycle or approximately fourfold increase in workload. Free ADP levels calculated for each voxel showed that ADP was relatively higher in the subendocardium than the subepicardium, and in all transmural layers was higher than its apparent Km for oxidative phosphorylation. In this domain changes in ADP content with workload and MVO2 are not expected and were not observed.

Adenosine Diphosphate↗
PubMed1990

Correlation between transmural high energy phosphate levels and myocardial blood flow in the presence of graded coronary stenosis.

Spatially localized nuclear magnetic resonance spectroscopy was used to investigate with transmural differentiation the response of myocardial high energy phosphate compounds and inorganic orthophosphate (Pi) to graded reductions in coronary blood flow caused by sustained coronary stenosis. In an open-chest model, localized 31P nuclear magnetic resonance spectra from five layers across the left ventricular wall were obtained simultaneously with transmural blood flow measurements during control conditions and during sustained graded reductions in intracoronary pressure. Both the blood flow, and high energy phosphate and Pi contents displayed transmural heterogeneity in response to decreases in intracoronary pressure. The subendocardial creatine phosphate (CP) level remained unchanged as blood flow was reduced to approximately 0.7 ml/min/g wet wt and decreased precipitously beyond this critical flow level. The relation between CP and flow in the midmyocardium and especially in the subepicardium was more complex. Subepicardial CP content did not correlate well with blood flow; however, in cases in which a coronary stenosis resulted in subendocardial hypoperfusion but subepicardial flow was near or above normal, a close correlation was present between subepicardial and subendocardial CP levels. ATP levels in all layers remained unaltered until blood flow was severely reduced. These results demonstrate that 1) the myocardial high energy phosphate and Pi levels at any transmural layer are not generally determined by O2 and blood flow limitation under basal conditions; 2) during subtotal coronary occlusion, increased oxygen extraction is able to meet myocardial needs until a critical level of stenosis is reached; 3) below a critical flow level, subendocardial CP and Pi contents are closely correlated with absolute subendocardial blood flow; and 4) in the presence of a coronary stenosis, subepicardial CP and Pi contents may change even in the absence of perfusion deficit secondary to loss of subendocardial function.

Adenosine Triphosphate↗
PubMed1989

Spectroscopic imaging and spatial localization using adiabatic pulses and applications to detect transmural metabolite distribution in the canine heart.

Adiabatic pulses have been employed in spectroscopic imaging and relaxation rate measurements at 4.7 T to demonstrate the feasibility of obtaining spectroscopic data from the complete sensitive volume of a surface coil using the surface coil as a transmitter and receiver. With conventional B1 sensitive pulses, spectroscopic localization or imaging techniques, such as chemical-shift imaging, yield resonance intensities that are distorted severely as a function of space, and maximal signal is detected from a small region within the complete sensitive volume of the coil. With adiabatic pulses, however, this problem is eliminated completely. In addition, a new method of spatial localization is introduced. This method, referred to as FLAX-ISIS, is a derivative of longitudinally modulated Fourier series window and ISIS approaches and utilizes adiabatic inversion and excitation pulses. The method allows construction of localized spectra for multiple regions along the surface coil axis by postacquisition data manipulation of a single set of free induction decays. These techniques were applied to the study of the myocardium using an implanted surface coil in an instrumented closed-chest canine model and in an open-chest preparation. The results demonstrate that one-dimensional techniques are adequate for transmural detection of metabolites provided signal origin is restricted to a column perpendicular to the left ventricle wall.

Animals↗
PubMed1989

Transmural metabolite distribution in regional myocardial ischemia as studied with 31P NMR.

Phosphorus-31 nuclear magnetic resonance (31P NMR) has been applied to study the canine heart prior to and during regional myocardial ischemia induced by partial flow reduction in the left anterior descending coronary artery (LAD). NMR data were acquired in a transmural fashion by restricting the signal to a column perpendicular to the heart wall using B0 gradients and obtaining spectroscopic spatial resolution along the third dimension using the B1 gradient and adiabatic excitation. With this approach, transmural spectra were accumulated in five separate voxels spanning the wall of the left ventricle from the epicardium to the endocardium. In the normal canine myocardium the levels of high-energy phosphates CP and ATP were relatively constant throughout the left ventricular wall, with only minor evidence of free inorganic phosphate in any of the transmural voxels. However, during sustained partial occlusion of the LAD, significant regional differences between the epi- and the endocardium were noted. The data demonstrate the importance of studying cardiac bioenergetics with transmural differentiation.

Animals↗
PubMed1989

Metabolic consequences of coronary stenosis. Transmurally heterogeneous myocardial ischemia studied by spatially localized 31P NMR spectroscopy.

Coronary stenosis results in transmurally non-uniform blood flow with the inner layers of the left ventricular wall typically suffering a more severe hypoperfusion relative to the outer layers. Coupled with numerous other transmural non-uniformities such as systolic tension development and oxygen needs, the heterogeneous blood flow distribution in the presence of coronary stenosis is expected to result in transmurally heterogeneous ischemia. All previous NMR spectroscopy studies of myocardial metabolism and bioenergetics under normal and ischemic conditions treated the organ as a homogeneous tissue. We have utilized spatially localized 31P NMR spectroscopy together with non-NMR measurements of regional blood flow to study the myocardium with transmural spatial differentiation under normal and flow-restricted conditions. 31P NMR and blood flow data obtained concurrently on each heart revealed that sustained coronary artery stenosis resulted in transmurally non-uniform ischemia which largely paralleled the hypoperfusion pattern. The reduction in creatine phosphate content (with consequent elevation of Pi) and hypoperfusion was tightly correlated in the subendocardium for flow rates less than approximately 0.7 mL/min per g wet myocardium. The high energy phosphate and Pi content of the epicardium, however, was responsive not only to the flow to this region but also to the extent of ischemia in the subendocardial layers. These results document the utility of localized NMR spectroscopy in physiologic research and suggest potential biomedical applications due to the tight correlation noted between alterations in blood flow and changes in the phosphorylated metabolite levels detected by 31P NMR.

Animals↗
PubMed1988

31P NMR probes of sipunculan erythrocytes containing the O2-carrying protein hemerythrin.

Reported are the first examinations by 31P NMR of erythrocytes containing the non-heme iron O2-carrying protein hemerythrin (Hr). Intact coelomic erythrocytes from the sipunculids Phascolopsis gouldii and Themiste zostericola were shown by 31P NMR to contain O-phosphorylethanolamine and 2-aminoethylphosphonate as the major soluble phosphorus metabolites. This combination of major metabolites appears to be unique to sipunculan erythrocytes. Nucleoside triphosphates and mannose 1-phosphate were present in lower concentrations. The concentration of O-phosphorylethanolamine within P. gouldii erythrocytes was established to be greater than 20 mM. T. zostericola erythrocytes contained relatively high levels of 2-aminoethylphosphonate (on the order of 0.1 M) and lower levels of O-phosphorylethanolamine compared with those of P. gouldii. For P. gouldii and T. zostericola the intracellular pHs were determined to be 7.2 +/- 0.1 and 7.1 +/- 0.1, respectively, in air-equilibrated erythrocytes, and 6.5 +/- 0.1 in anaerobic P. gouldii erythrocytes. O-Phosphorylethanolamine was found to bind weakly to P. gouldii metHr (Kf approximately 7 M-1). This interaction is best characterized by either negative cooperativity or nonspecific binding. O-Phosphorylethanolamine strongly inhibits azide binding to the iron site of P. gouldii metHr at pH 7.2. The rate of azide binding decreases by approximately 85-fold in the presence of 0.33 M O-phosphorylethanolamine. However, neither O-phosphorylethanolamine nor 2-aminoethylphosphonate at 0.33 M was found to have any significant effect on O2 affinity of P. gouldii deoxyHr. Alternative functions for the two metabolites are suggested.

Animals↗
PubMed1987

31P NMR studies of ATP synthesis and hydrolysis kinetics in the intact myocardium.

The origin of the nuclear magnetic resonance (NMR)-measurable ATP in equilibrium Pi exchange and whether it can be used to determine net oxidative ATP synthesis rates in the intact myocardium were examined by detailed measurements of ATP in equilibrium Pi exchange rates in both directions as a function of the myocardial oxygen consumption rate (MVO2) in (1) glucose-perfused, isovolumic rat hearts with normal glycolytic activity and (2) pyruvate-perfused hearts where glycolytic activity was reduced or eliminated either by depletion of their endogenous glycogen or by use of the inhibitor iodoacetate. In glucose-perfused hearts, the Pi----ATP rate measured by the conventional two-site saturation transfer (CST) technique remained constant while MVO2 was increased approximately 2-fold. When the glycolytic activity was reduced, the Pi----ATP rate decreased significantly, demonstrating the existence of a significant glycolytic contribution. Upon elimination of the glycolytic component, the measured Pi----ATP rates displayed a linear dependence on MVO (micromoles of O consumption rate) with a slope of 2.36 +/- 0.15 (N = 8, standard error of the mean). This linear relationship is expected if the rate determined by CST is the net rate of ATP synthesis by the oxidative phosphorylation process, in which case the slope must equal the P:O ratio. The ATP----Pi rates and rate:MVO ratios measured by the multiple-site saturation transfer method at two MVO2 levels were equal to the corresponding Pi----ATP rates and rate:MVO ratios obtained in the absence of a glycolytic contribution. The following conclusions are drawn from these studies: (1) unless the glycolytic contribution to the ATP in equilibrium Pi exchange is inhibited or is specifically shown not to exist, the myocardial Pi in equilibrium ATP exchange due to oxidative phosphorylation cannot be studied by NMR; (2) at moderate MVO2 levels, the reaction catalyzed by the two glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase is near equilibrium; (3) the ATP synthesis by the mitochondrial H+-ATPase occurs unidirectionally (i.e., the reaction is far out of equilibrium); (4) the "operative" P:O ratio in the intact myocardium under our conditions is significantly less than the canonically accepted value of 3.

Adenosine Triphosphate↗
PubMed1987

Phosphorus-31 nuclear magnetic resonance studies of spermatozoa from the boar, ram, goat and bull.

1. Phosphorus-31 nuclear magnetic resonance spectroscopy (31P-NMR) was utilized to examine semen and spermatozoa isolated from boars, rams, goats and bulls. 2. Whole semen was found to contain high but variable levels of glycerylphosphocholine, most of which was located in the seminal plasma rather than in the spermatozoa. 3. Spermatozoa concentrated into a pellet were found to contain resonances for inorganic phosphate, phosphomonoesters including fructose-1,6-bisphosphate and glucose-6-phosphate, and free nucleotide triphosphate peaks. 4. A broad resonance was observed from 30 to -25 ppm which originated partly from nucleotide tri- and diphosphates. 5. No high energy molecules such as phosphoarginine or phosphocreatine which could act as energy shuttles were observed.

Animals↗
PubMedDate not supplied

Acquisition of human multislice MR images at 8 Tesla.

PURPOSE: The purpose of this work was to acquire high quality multislice MR images from the human brain at 8 Tesla (T). METHOD: Initial images were acquired with an 8 T/80 cm magnet designed and manufactured by Magnex Scientific (Abingdon, England). Images were acquired using volume RF coils operating at 340 MHz. A torque-free head gradient insert was utilized to spatially encode the spins. Images were acquired from the human head using gradient-recalled echo pulse sequences. RESULTS: Ultra high frequency (UHF) MR images have been obtained from the human head that display both excellent signal/noise ratio and image quality. The power required to obtain the 8 T images was much less than expected based on the trend obtained at lower fields. CONCLUSION: In this work, we have demonstrated that it is possible to obtain high quality multislice images from the human brain at 8 T. These images display the phenomenal potential for imaging at UHF and reveal that none of the stumbling blocks advanced by the MR community for an 8 T project (RF penetration, dielectric effects, specific absorption rate problems, RF power requirements) proved to be a limitation.

Brain↗
PubMedDate not supplied

Design and assembly of an 8 tesla whole-body MR scanner.

PURPOSE: The purpose of this report is to describe the design and construction of an 8 T/80 cm whole-body MRI system operating at 340 MHz. METHOD: The 8 T/80 cm magnet was constructed from 414 km of niobium titanium superconducting wire. The winding of this wire on four aluminum formers resulted in a total inductance of 4,155 H. Gradient subsystems included either a body gradient or a head gradient along with a removable shim insert. The magnet and gradient subsystems were interfaced to two spectrometers. These provided the control of the gradient amplifiers and the two sets of four RF power amplifiers. The latter provide in excess of 8 kW of RF power from 10 to 140 MHz and 10 kW of RF power from 245 to 345 MHz. A dedicated computer-controlled patient table was designed and assembled. The entire system is located in a clinical setting, facilitating patient-based studies. RESULTS: The 8 T/80 cm magnet was energized without complication and achieved persistent operation using 198.9 A of current, thereby storing 81.5 MJ of magnetic energy. Exceptional performance was observed for nearly all components both in isolation and when combined within the complete system. CONCLUSION: An 8 T/80 cm MRI system has been assembled. The magnet subsystem is extremely stable and is characterized by good homogeneity and acceptable boil-off rates.

Aluminum↗
PubMedDate not supplied

Dielectric resonance phenomena in ultra high field MRI.

PURPOSE: Dielectric resonances have previously been advanced as a significant cause of image degradation at higher fields. In this work, a study of dielectric resonances in ultra high field MRI is presented to explore the real importance of dielectric resonances in the human brain in this setting. METHOD: Gradient-recalled echo images were acquired using a transverse electromagnetic resonator at 1.5, 4.7, and 8 T. Images were obtained from the human head and from phantoms filled with pure water, saline, and mineral oil. In addition, an exact theoretical analysis of dielectric resonances is presented for a spherical phantom and for a model of the human head. RESULTS: Theoretical results demonstrate that distilled water can sustain dielectric resonances in head-sized spheres near 200 and 360 MHz, but the presence of significant conductivity suppresses these resonances. These findings are confirmed experimentally with proton images of water and saline (0.05 and 0.125 M NaCl). For lossy phantoms, coupling between the source and phantom overwhelms the dielectric resonance. Because of their low relative permittivity, mineral oil phantoms with 20 cm diameter do not exhibit dielectric resonances below approximately 900 MHz. Significant dielectric resonances were not observed in human head images obtained at 1.5, 4.7, and 8 T.

Algorithms↗
PubMedDate not supplied

Macroscopic susceptibility in ultra high field MRI.

PURPOSE: Magnetic susceptibility provides the basis for functional studies and image artifacts in MRI. In this work, magnetic susceptibility and the associated artifacts were analyzed at 8 T in phantoms and in the human head. METHOD: A mineral oil phantom was constructed in which three cylindrical air-filled tubes were inserted. This phantom was analyzed with gradient-recalled echo and SE imaging techniques acquired using varying TEs and receiver bandwidths. To visualize the presence of magnetic susceptibility artifacts in the head at 8 T, near axial, coronal, and sagittal GE images were also acquired from human volunteers. RESULTS: The use of gradient-recalled echo imaging resulted in the production of significant magnetic susceptibility artifacts. These artifacts could be readily visualized in phantom samples containing air-filled cylindrical tubes. In the human head, susceptibility artifacts produced significant image distortion in the skull base region. In this area, susceptibility artifacts often resulted in the complete loss of MR signal. Magnetic susceptibility artifacts were manifested as bands of varying signal intensity in the frontal lobe and temporal bone region. In addition, they produced clear distortions in the appearance of brain vasculature and seemed to accentuate the relative size of venous structures within the brain. CONCLUSION: When using gradient-recalled echo imaging in combination with relatively long TE values, magnetic susceptibility artifacts can be severe at 8 T. These artifacts could be reduced by increasing receiver bandwidths and by lowering effective TEs. As ultra high field MRI provides a fertile ground for the study of susceptibility artifacts in MRI, improvements obtained at this field strength will have a direct impact on studies performed at lower field strengths.

Air↗