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Biomedical subjects

C J Hardy

Publications and source records attributed to C J Hardy.

At least 37 records · Page 2Linked to original sources

Measurement of body surface area in children with liver disease by a novel three-dimensional body scanning device.

Body surface area (BSA) is used in paediatrics to assess fluid requirement, drug doses, cardiac output and glomerular filtration rate. The aim of this study was to examine, in children with liver disease, the relationship between BSA determined by a traditional nomogram and BSA measured by a novel three-dimensional technique--Loughborough Anthropometric Shadow Scanner (LASS). Subjects were 16 children, mean age 8.1 (range 3.6-14.9) years, with a variety of liver diseases. Twenty-eight controls had a mean age of 7.1 (3.1-10.5) years. All had LASS scans performed as well as 21 anthropometric measurements taken by a single observer. There was a significant relationship between BSA (LASS) and BSA nomogram for liver-diseased children (r = 0.99) and controls (r = 0.96). The BSA nomogram values were significantly greater (P < 0.05) than BSA (LASS) for liver-diseased subjects by 10.1% (-0.35 to +20.6; 95% confidence interval), and for controls by 9.6% (4.1-23.2). Best prediction of BSA (LASS) for liver-disease subjects used height, body weight and gluteal furrow circumference [r2 = 0.997; standard estimated error (SEE) = 0.015 m2] and for controls used body weight alone (r2 = 0.907; SEE = 0.048 m2). BSA nomogram has no additional error in children with liver disease, but may overestimate BSA by 10% compared with a novel three-dimensional body surface scanning technique.

Adolescent↗

Brain and cerebrospinal fluid motion: real-time quantification with M-mode MR imaging.

PURPOSE: To assess motion of brain parenchyma and cerebrospinal fluid (CSF) with magnetic resonance (MR) phase imaging in real time. MATERIALS AND METHODS: Repetitive excitation of a cylinder with two-dimensional selective excitation followed by one-dimensional imaging along the cylinder axis yielded profiles analogous to those of M-mode echography. Bipolar gradients provided velocity sensitivity in an arbitrary spatial direction. RESULTS: Brain and CSF of healthy volunteers exhibited periodic motion in the frequency range of normal heart rate. Both brain hemispheres showed periodic squeezing of the ventricles, with peak velocities up to 1 mm/sec followed by a slower recoil. Superimposed on the regular displacement of the brain stem was a slow, respiratory-related periodic shift of the neutral position. During the Valsalva maneuver, the brain stem showed initial caudal and subsequent cranial displacement of 2-3 mm. Coughing produced a short swing of CSF in the cephalic direction. CONCLUSION: Real-time MR phase imaging allows observation of non-periodic events in brain and CSF motion.

Adult↗

An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET.

OBJECTIVES: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. DESIGN: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. PATIENTS: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. RESULTS: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. CONCLUSIONS: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.

Aged↗

Real-time acquisition, display, and interactive graphic control of NMR cardiac profiles and images.

A highly interactive MRI scanner interface has been developed that allows, for the first time, real-time graphic control of one-dimensional (1D) and two-dimensional (2D) cardiac MRI exams. The system comprises a Mercury array processor (AP) in a Sun SPARCserver with two connections to the MRI scanner, a data link that passes the NMR data directly to the AP as they are collected, and a control link that passes commands from the Sun to the scanner to redirect the imaging pulse sequence in real time. In the 1D techniques, a cylinder or "pencil" of magnetization is repeatedly excited using gradient-echo or spin-echo line-scan sequences, with the magnetization read out each time along the length of the cylinder, and a scrolling display generated on the Sun monitor. Rubber-band lines drawn on the scout image redirect the pencil or imaging slice to different locations, with the changes immediately visible in the display. M-mode imaging, 1D flow imaging, and 2D fast cardiac imaging have been demonstrated on normal volunteers using this system. This platform represents an operator-"friendly" way of directing real-time imaging of the heart.

Computer Systems↗

Proton Overhauser enhancements in human cardiac phosphorus NMR spectroscopy at 1.5 T.

Narrowband irradiation of water protons with a surface coil yields significant nuclear Overhauser enhancement (nOe) of phosphocreatine (PCr) and some adenosine triphosphate (ATP) moieties in localized and unlocalized phosphorus (31P) NMR spectra from chest and heart muscle. In seven normal subjects at 1.5 T the nOe values were 0.6 +/- 0.3, 0.6 +/- 0.3, 0 +/- 0.3, and 0.3 +/- 0.2 for myocardial PCr, gamma-ATP, alpha-ATP, and beta-ATP, respectively, not significantly different from those in chest muscle. Distortion of the measured PCr/ATP ratios due to differences in the nOe may require accurate correction to realize the full benefit of the effect in studies involving quantitative intergroup comparisons.

Adenosine Triphosphate↗

An NMR phased array for human cardiac 31P spectroscopy.

A four-coil phased-array 31P NMR receiver was designed and tested for human cardiac applications, to determine whether the combination of relatively high signal-to-noise ratio (SNR) and large field of view produced in 1H imaging is also realized for in vivo 31P spectroscopy. Spectra were acquired in parallel from an array of four overlapping 6.5-cm surface coils using one- and two-dimensional phase-encoding pulse sequences and were optimally combined to yield composite spectroscopic images. The phased array was found to generate useful 31P spectra from a 2.5-fold wider lateral region around the anterior myocardium than a single receiver of the same size as the array elements, with no increase in imaging time. In addition, the sensitive depth was increased by up to 2 cm over that of a single coil. Spectra could be acquired in roughly 15 min from a region extending to the middle of the heart, with voxel sizes of 2 x 2 x 4 cm3. For the average heart voxel, the SNR of the combined spectrum was higher than that of the best spectrum from any one coil in the array by 30%, with some voxels showing an increase as high as 60%.

Heart↗

Alzheimer dementia: quantification of energy metabolism and mobile phosphoesters with P-31 NMR spectroscopy.

To determine whether high-energy phosphate metabolism and mobile phosphoester indexes of membrane metabolism are altered in Alzheimer disease and to help resolve some inconsistencies in the literature, brain phosphate metabolite concentrations and ratios were measured in 11 patients with mild to severe dementia of the probable Alzheimer type and 14 healthy subjects. Fully relaxed, spatially localized, phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) MR imaging were performed. No significant differences were found in the concentrations and relative ratios of phosphocreatine, nucleoside triphosphate, inorganic phosphate, phosphomonoester, and phosphodiesters in whole axial sections through the lateral cerebral ventricles of the brain that could not be accounted for by atrophy. There was no correlation between P-31 NMR indexes and the severity of dementia as assessed with neuropsychologic testing. High-energy phosphate and membrane metabolism, as detected in vivo with P-31 NMR spectroscopy in whole-brain sections, do not appear to play a major role in the disease process, except as a direct consequence of atrophy quantified with H-1 MR imaging.

Aged↗

31P spectroscopic localization using pinwheel NMR excitation pulses.

Spectroscopic imaging with a one-dimensional phase-encoding gradient and surface-coil reception relies on the restricted range of sensitivity of the surface coil to provide localization in the dimensions transverse to the coil axis and consequently suffers from relatively poor localization in these dimensions. A two-dimensional (2D) cylindrically selective excitation pulse with a large spectral bandwidth is presented here to remedy this problem. The gradient waveforms are derived from multiple spirals in k space which form an overall pinwheel pattern, resulting in a pulse which is much shorter than the equivalent single-spiral trajectory. Nonuniform traversal of the spirals further reduces the pulse width under conditions of gradient slew-rate limitations, yielding overall gains in bandwidth of up to about 30 compared with the equivalent single-spiral trajectory traversed at constant angular rate. The accompanying rf waveform is obtained by weighted 2D Fourier transformation of the desired sensitivity profile. A new weighting factor is introduced into the rf waveform to compensate for nonuniform sampling of k space by the pinwheel near the origin. This factor is independent of the weighting used to account for the rate of traversal of the trajectory and is applicable to 2D pulse design in general. Pulse sequences employing pinwheel excitation in conjunction with either phase-encoding or slice-selective inversion are used to produce multiple-voxel and single-voxel localization in a human heart and a phantom. Pinwheel pulses may be used to advantage on moieties with long spin-lattice relaxation times and short transverse relaxation times and are therefore ideal for applications in phosphorus (31P) NMR.

Heart↗

Fast MR cardiac profiling with two-dimensional selective pulses.

A rapid-profiling NMR pulse sequence has been designed to provide an interactive, real-time cardiac probe analogous to M-mode ultrasound. The pulse sequence employs a two-dimensional (2D) selective NMR pulse to excite a narrow (nominally 1-cm-diameter) cylinder of magnetization intersecting the heart. This procedure is followed by a readout gradient applied along the length of the cylinder, or "beam," to yield an M-mode type profile with a one-dimensional Fourier transform reconstruction. k-space techniques were used to design 2D pulses which excite cylinders characterized by either Gaussian or square radial excitation profiles. Images of phantoms acquired at 1.5 T confirm the predictions of the k-space analysis. The cylinder can be displaced interactively by modulating the rf excitation and the beam axis can be reoriented to any oblique direction by changing the relative mixing of the gradient waveforms. Flow compensation using bipolar gradient waveforms inverts the contrast of flowing blood and suppresses flow artifacts. A gated cardiac image is acquired as a reference to locate the excitation axis. A series of cardiac experiments was performed on several healthy volunteers. As the beam is moved and rotated to probe the myocardium, the profile plots resemble an M-mode echocardiogram. Unlike in M-mode echocardiography, however, the axis of interrogation is not limited to specific windows, and there is distinct flexibility of contrast. However, the temporal resolution is currently less than that achieved by ultrasound. NMR M-mode profiling provides a direct, fast method of measuring heart motion to assess cardiac function as part of an MR cardiac exam.

Fourier Analysis↗

Quantitative measurement of blood flow using cylindrically localized Fourier velocity encoding.

A procedure for the quantitative measurement of blood velocity was developed and evaluated in the portal vein, aorta, and vena cava of healthy volunteers. This procedure utilizes Fourier velocity encoding and can be performed with or without cardiac gating. The accuracy of velocity measurements is determined by the accuracy of the gradient subsystem. Flow measurements derived from the velocity measurement are further limited in their accuracy by the luminal cross-section measurement. Spatial localization is accomplished with an excitation pulse having a cylindrical rather than slab geometry. Data are acquired in the presence of a readout gradient to provide resolution along the cylindrical axis.

Aorta↗

Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy.

Myocardial high-energy phosphate metabolism in patients with dilated cardiomyopathy (DCM) of ischemic or idiopathic etiology was assessed at rest by one-dimensional phase-encoded 31P-nuclear magnetic resonance (NMR) spectroscopy studies performed in conjunction with 1H imaging in 20 patients with DCM and in 12 normal volunteers. The measured values of anterior myocardial phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP), corrected for partial saturation and contamination of the spectra by blood metabolites, averaged 1.80 +/- 0.06 (mean +/- SE) in normal volunteers and 1.46 +/- 0.07 in the patients overall, a highly significant (p less than 0.001) decrease. In patients with DCM accompanied by coronary artery disease (n = 9), the PCr/beta-ATP ratio averaged 1.53 +/- 0.07, while in those with DCM alone it was 1.41 +/- 0.12 (n = 11), a value that was not significantly different. There was no significant correlation (r = 0.34) between myocardial PCr/ATP ratio and left ventricular ejection fraction in patients. These studies demonstrate that myocardial PCr/ATP ratios are reduced at rest in human ischemic and idiopathic dilated cardiomyopathy.

Adenosine Triphosphate↗

Myocardial high-energy phosphate metabolism and allograft rejection in patients with heart transplants.

To determine whether myocardial high-energy phosphate metabolism is altered in cardiac allograft patients undergoing rejection, 14 patients with heart transplants were examined with image-guided, one-dimensional, phase-encoded surface-coil phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy on 19 occasions 39-2,021 days after transplantation. On average, patients underwent mild rejection (detected with endomyocardial biopsy) and had a reduced ratio of anterior myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) (1.57 +/- 0.50 [standard deviation] vs 1.93 +/- 0.2; P less than .01) compared with that of 17 healthy control subjects. Ratios of PCr to inorganic phosphate also appeared lower whenever detectable. However, P-31 NMR spectroscopy did not permit reliable identification of patients who required augmented therapy for rejection detected with biopsy either on the day of the P-31 NMR spectroscopic study or at the next scheduled biopsy 10-140 days thereafter (sensitivity, 50%, and specificity, 73% with use of cardiac-averaged PCr/ATP values for each heart; sensitivity, 88%, and specificity, 55% with use of the lowest myocardial PCr/ATP ratios measured in each heart).

Adenosine Triphosphate↗

Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease.

BACKGROUND: The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. METHODS: To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. RESULTS: The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (greater than or equal to 70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45 +/- 0.31 at rest to 0.91 +/- 0.24 during exercise (P less than 0.001) and recovered to 1.27 +/- 0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60 +/- 0.20 at rest and 1.62 +/- 0.18 during exercise (P not significant), as compared with 1.51 +/- 0.19 at rest and 1.02 +/- 0.26 during exercise before revascularization (P less than 0.02). CONCLUSIONS: The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with 31P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment.

Adenosine Triphosphate↗

Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance.

Cardiac-gated phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopic imaging with surface coils resolves in three dimensions the spatial distribution of high energy phosphate metabolites in the human heart noninvasively. 31P spectra derive from 6- to 14-cm3 volumes of myocardium in the anterior left ventricle, septum, and apex, at depths of up to about 8 cm from the chest, as identified by proton (1H) NMR anatomical images acquired without moving the subject. Spectroscopic images are acquired in 9 to 21 min at 1.5 T. Metabolite concentrations are quantified with reference to a standard located outside the chest, yielding normal in vivo concentrations of phosphocreatine and adenosine triphosphate of about 11.0 +/- 2.7 (SD) and 6.9 +/- 1.6 mumol/g of wet heart tissue, respectively. High energy phosphate contents did not vary significantly with location in the normal myocardium, but 2,3-diphosphoglycerate signals from blood varied with subject and location.

Adenosine Triphosphate↗

Continual NMR cardiography without gating: M-mode MR imaging.

A magnetic resonance (MR) pulse sequence was designed and implemented to examine the heart continually without gating, at rates in excess of 256 images in 7 seconds. The results are analogous to those of M-mode ultrasound, allowing interactive exploration of cardiac dynamics and flow in real time with full three-dimensional freedom of view. The technique is based on designed two-dimensional excitation pulses in which the magnetic field gradient is not constant, as in section-selection pulses, but varies in time to define a trajectory that results in a specified (eg, cylindric) region of excitation. The technique was implemented on a 1.5-T clinical imager with no special hardware and was tested on phantoms and volunteers. In human subjects, details of valve motion, intracardiac flow, and wall motion could be observed from moment to moment along optimal lines of sight selected interactively, with or without flow compensation and without gating. The momentary physiologic changes in chamber volumes and blood pool replenishment that occur during rhythm disturbances, the Valsalva maneuver, and simple breathing and breath-holding were readily demonstrated.

Adult↗

AIDS dementia complex: brain high-energy phosphate metabolite deficits.

To test whether compromised high-energy phosphate metabolism is implicated in the neurologic impairment of acquired immunodeficiency syndrome dementia complex (ADC), brain phosphate metabolite concentrations and ratios were measured noninvasively in 12 patients with mild to moderate ADC and 29 healthy volunteers by use of localized phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) magnetic resonance (MR) imaging. In patients, brain phosphocreatine (PCr) and nucleoside triphosphate (NTP) concentrations in sections through the centrum semiovale that were seen with NMR spectroscopy were reduced significantly from normal values of 4.92 mmol/kg wet weight +/- .13 (standard error of the mean) and 2.79 mmol/kg +/- .11, respectively, to 3.33 mmol/kg +/- .26 and 1.99 mmol/kg +/- .13 (P less than .0001). The ratios of metabolites detectable with P-31 NMR spectroscopy did not differ significantly from those of control subjects. The magnitude of the PCr and NTP deficits in ADC was not explicable by focal abnormalities or cerebral atrophy quantified in images of the same regions. These results are consistent with the hypothesis of a generalized virus-associated toxic process affecting brain cell function in ADC. Noninvasive measurement of metabolite concentrations with NMR spectroscopy provides new functional information that may help quantify disease progression and response to therapy.

AIDS Dementia Complex↗

Proton-decoupled, Overhauser-enhanced, spatially localized carbon-13 spectroscopy in humans.

Spatially localized, natural abundance, carbon (13C) NMR spectroscopy has been combined with proton (1H) decoupling and nuclear Overhauser enhancement to improve 13C sensitivity up to five-fold in the human leg, liver, and heart. Broadhand-decoupled 13C spectra were acquired in 1 s to 17 min with a conventional 1.5-T imaging/spectroscopy system, an auxiliary 1H decoupler, an air-cooled dual-coil coplanar surface probe, and both depth-resolved surface coil spectroscopy (DRESS) and one-dimensional phase-encoding gradient NMR pulse sequences. The surface coil probe comprised circular and figure-eight-shaped coils to eliminate problems with mutual coupling of coils at high decoupling power levels applied during 13C reception. Peak decoupler RF power deposition in tissue was computed numerically from electromagnetic theory assuming a semi-infinite plane of uniform biological conductor. Peak values at the surface were calculated at 4 to 6 W/kg in any gram of tissue for each watt of decoupler power input excluding all coil and cable losses, warning of potential local RF heating problems in these and related experiments. The average power deposition was about 9 mW/kg per watt input, which should present no systemic hazard. At 3 W input, human 13C spectra were decoupled to a depth of about 5 cm while some Overhauser enhancement was sustained up to about 3 cm depth, without ill effect. The observation of glycogen in localized natural abundance 13C spectra of heart and muscle suggests that metabolites in the citric acid cycle should be observable noninvasively using 13C-labeled substrates.

Carbon Isotopes↗

Problems and expediencies in human 31P spectroscopy. The definition of localized volumes, dealing with saturation and the technique-dependence of quantification.

Several technological problems in in vivo localized spectroscopy of metabolism are discussed in the context of comparing data obtained by different means. Deficiencies in spectroscopy localization methods can produce spectra that are dominated by artefactual signals derived from outside of selected volumes. Such artefacts are not usually correctly accounted for by representations of the profiles of the transverse magnetization alone. Selected sensitive volumes should be defined in terms of the size of tissue contributing the major fraction of signal to an observed spectrum, which is the integrated response from the sample including any phase cancellation effects. Phase cancellation in one-dimensional localization techniques employing excitation by an RF field with uniform phase distribution and surface coil detection such as depth resolved surface coil spectroscopy, chemical shift imaging (CSI) and rotating frame zeugmatography (RFZ) can significantly alter the effective radius of the sensitive volumes depending on the sample distribution and the extent of the homogeneous region of the magnet. Also, discrete spatial sampling in RFZ and CSI can radiate signal artefacts of around 25% into adjacent elements depending on the location and distribution of signal sources. Acquisition delays between excitation and detection and partial saturation are other major sources of systematic error. Saturation factors for metabolites are not easily obtainable on localized volumes during clinical exams on an individual basis, but may be expediently obtained as larger-volume tissue-averages. Better documentation of saturation effects, acquisition delays and localized volume sizes is needed to compare and validate clinical results and performance.

Brain↗