Biomedical subjects

D J Meyerhoff

Publications and source records attributed to D J Meyerhoff.

50 records · Page 3Linked to original sources

PubMed1991

P-31 spectroscopy study of response of superficial human tumors to therapy.

Studies were performed to characterize phosphorus-31 magnetic resonance (MR) spectra obtained from 10 superficial human tumors outside the brain and to determine whether P-31 MR spectroscopy could allow detection of a response to therapy before a change in tumor size was measured. The ratio of phosphomonoester to adenosine triphosphate peak intensities (PME/ATP) was unusually large in all tumors studied. The average PME/ATP in lymphomas (1.8 +/- 0.5) was greater than in nonlymphoma cancers (1.1 +/- 0.15). The average PME/ATP for all tumors studied (1.4 +/- 0.5) was much greater than that of underlying skeletal muscle (0.23 +/- .09). Eight of the tumors were studied before and after therapy. Responders were distinguished from nonresponders on the basis of changes in tumor size. PME/ATP decreased during therapy in three lymphomas that responded to therapy. In an adenocarcinoma and Ewing sarcoma that did not respond to therapy, PME/ATP increased. PME/ATP remained constant in two squamous cell carcinomas that responded to therapy and decreased in one squamous cell carcinoma that decreased in size by 40% but was classified as a nonresponder. Changes in PME/ATP did not always parallel changes in tumor size during therapy. In two patients, a decrease in PME/ATP preceded a decrease in tumor size. In four patients, PME/ATP increased transiently during periods when tumor size remained constant.

Adenosine Triphosphate↗

PubMed1990

Comparison of 31P MRS and 1H MRI at 1.5 and 2.0 T.

The goals of this study were to compare 31P magnetic resonance spectroscopy (MRS) and 1H magnetic resonance imaging (MRI) of human subjects and phantoms at 1.5 and 2.0 T. The 31P signal-to-noise (S/N) ratios in phantom standards and in localized volumes in human brain and liver were compared at 1.5 and 2.0 T. In addition, T1 values for 31P resonances in human brain, 31P linewidths of metabolites in human brain and liver, 1H S/N in a phantom standard, and MR image quality in human head and body were compared at the two field strengths. The results of our study showed that at the higher strength field, (1) in vivo 31P MRS studies benefited from up to 32% improvement in S/N; (2) in vivo 31P MRS studies also benefited from increased spectral dispersion; (3) the quality of MR head images remained comparable; and (4) body images showed some decrease in image quality due to increased chemical shift, and flow and motion artifacts.

Brain↗

PubMed1990

Non-invasive quantitation of human liver metabolites using image-guided 31P magnetic resonance spectroscopy.

Phosphorus-containing metabolites in normal human liver have been quantitated non-invasively with 31P magnetic resonance spectroscopy using surface coils. The location of the volume of interest (VOI) was defined by 1H magnetic resonance imaging. Subsequently, a modified three-dimensional localization technique (ISIS) was used to acquire 31P magnetic resonance spectra from the VOI. To account for partial saturation produced by rapid signal averaging, the spin/lattice relaxation times (T1) of all hepatic phosphorus resonances were measured. The corrected resonance integrals were used to derive absolute molar concentrations for the following hepatic metabolites (mmol/kg wet weight): ATP, 2.0; inorganic phosphate, 2.1; phosphodiesters, 5.4; and phosphomonoesters, 0.9. These values are compared with previously reported values for humans using freeze-clamping techniques, and provide a basis for comparison with studies of hepatic disease in this laboratory.

Adenosine Triphosphate↗

PubMed1990

Image-guided 31P magnetic resonance spectroscopy of normal and transplanted human kidneys.

Image-guided 31-phosphorus magnetic resonance spectroscopy (MRS) was used to obtain spatially localized 31P spectra of good quality from healthy normal human kidneys and from well-functioning renal allografts. A surface coil of 14 cm diameter was used for acquiring phosphorus signals solely from a volume-of-interest located within the kidney. To determine the effects of kidney transplantation on renal metabolism, patients with well functioning allografts were studied. Little or no phosphocreatine in all spectra verifies the absence of muscle contamination, and is consistent with proper volume localization. The intensity ratio of phosphomonoesters (PME) to adenosine triphosphate (ATP) resonances in transplanted kidneys (PME/ATP = 1.1 +/- 0.4) was slightly elevated (P = 0.2) compared to that of healthy normal kidneys (PME/ATP = 0.8 +/- 0.3). The inorganic phosphate (Pi) to ATP ratio was similar in the two groups (Pi/ATP = 1.1 +/- 0.1 in transplanted kidneys vs. 1.2 +/- 0.6 in normal kidneys). Acid/base status, as evidenced from the chemical shift of Pi, was the same in both normal controls and transplanted kidneys. Despite the practical problems produced by organ depth, respiratory movement, and tissue heterogeneity, these results demonstrate that image-guided 31P MR spectra can reliably be obtained from human kidneys.

Adult↗

PubMed1990

P-31 MR spectroscopy of normal human brain and brain tumors.

Image-guided phosphorus-31 magnetic resonance (MR)-localized image-selected in vivo spectroscopy was performed on normal human brain and brain tumors. Peak area ratios, absolute molar concentrations of metabolites, and pH were determined. T1 values in normal brain were measured. The most important finding was that the metabolite concentrations detectable with MR spectroscopy in brain tumors were reduced from 20% to 70%. Phosphomonoesters, phosphodiesters, and phosphocreatine (PCr) showed the greatest decreases, while inorganic phosphate (Pi) showed the least change. The PCr-Pi ratio was significantly reduced in tumors. The pH of brain tumors (7.12 +/- 0.03) was more alkaline than that of normal brain (6.99 +/- 0.01). The authors conclude that the metabolite concentrations and pH in human brain tumors differ significantly from those in normal brain. These differences may be ultimately useful in characterizing tumors in man.

Adolescent↗

PubMed1990

Myocardial high-energy phosphates in reactive hyperemia.

This study used 31P nuclear magnetic resonance (NMR) spectroscopy to determine whether the magnitude and duration of myocardial reactive hyperemia (RH) reflect a commensurate derangement of myocardial high-energy phosphate (HEP) metabolism, or if coronary blood flow (CBF) and HEP metabolism are dissociated during RH. Twelve open-chest anesthetized pigs were studied during and after 24 s occlusion of the anterior descending coronary artery. CBF velocity was measured with a Doppler probe. NMR time resolution (4.8 s) was obtained by summing corresponding short blocks of data from multiple occlusions. During occlusion, phosphocreatine (PCr) declined to 65 +/- 5% (mean +/- SE) of control accompanied by increased spectral intensity of the Pi + phosphomonester region. By 20 s of reflow, HEPs had returned to control levels, but CBF was still elevated at 282 +/- 18% of control and remained elevated for an additional 53 +/- 7 s, during which 44 +/- 6% of total RH flow occurred. Therefore, the control of CBF is not closely coupled to the levels of myocardial HEPs during RH and the duration of RH does not reflect prolonged depletion of myocardial HEPs.

Animals↗

PubMed1990

Dynamic relation between myocardial contractility and energy metabolism during and following brief coronary occlusion in the pig.

Changes in high-energy phosphate metabolism may be important in the regulation of myocardial contractile function during ischemia. This study sought to determine the dynamic relation between myocardial contractile function and high-energy phosphate metabolism during and following brief (24-second) coronary occlusion, when large and rapid changes in both parameters occur. Eight anesthetized, open-chest pigs were instrumented with a Doppler flow probe and occluder on the anterior descending coronary artery, segment length crystals in the anterior left ventricular wall, and a surface coil for phosphorus-31 nuclear magnetic resonance spectroscopy. Phosphorus-31 spectra were reconstructed with a 4.8-second time resolution by summing corresponding short blocks of data from multiple occlusions. Metabolic and functional parameters were unchanged during the first 4.8 seconds of occlusion. During the remainder of occlusion, phosphocreatine progressively declined to 66 +/- 3% of control, inorganic phosphate rose to 170 +/- 8% of control, and segment shortening fell to 25 +/- 9% of control. A strong linear correlation was found between dynamic changes in segment shortening and phosphocreatine (r2 = 0.97), inorganic phosphate (r2 = 0.96), and the ratio of phosphocreatine to inorganic phosphate (r2 = 0.98) during occlusion. At any level of the ratio between phosphocreatine and inorganic phosphate, segment shortening was greater during reflow than during occlusion. The close, dynamic relation between segment shortening and phosphorus metabolites supports the regulation of contractility by changes in energy metabolism or its by-products during ischemia. During reactive hyperemia, the high coronary flow rate may be an independent factor modulating contractility.

Adenosine Triphosphate↗

PubMed1989

Phosphorus-31 magnetic resonance spectroscopy in humans by spectroscopic imaging: localized spectroscopy and metabolite imaging.

In in vivo phosphorus magnetic resonance spectroscopy (MRS), spectroscopic imaging (SI) can be used as a flexible localization technique, producing spectra from multiple volumes in a single examination. Presented here are phosphorus SI studies of human organs in which a selective-volume SI reconstruction was used rather than the usual array-format SI reconstruction. A linear predictor technique was used to estimate the initial points of the free induction decay missing because of the delay needed for phase-encoding gradients, significantly reducing the baseline artifacts which commonly complicate interpretation of SI spectra. In studies of heart, brain, liver, and kidney, the performance of SI was found to compare favorably with that of ISIS. SI phosphorus metabolite intensity images from a brain tumor patient were obtained at 2 X 2-cm in-plane resolution (with "slice" thickness of roughly 16 cm, determined by coil sensitivity) in 34 min, demonstrating the feasibility of obtaining clinically useful metabolite images in clinically reasonable examination times.

Astrocytoma↗

PubMed1989

Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach.

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMed1989

Abnormalities of the liver evaluated by 31P MRS.

Clinical phosphorus-31 magnetic resonance spectroscopy (31P MRS) of the liver requires the use of whole-body magnets and of spectroscopy techniques that acquire signal from defined volumes-of-interest within the liver. Such localization techniques and recent clinical studies are briefly reviewed. These studies indicate that (1) high phosphomonoester levels are present in liver diseases involving structural damage, and (2) that MRS of liver tumors may provide a sensitive and rapid indication of response to cancer therapy. Abnormalities of the liver such as alcoholic liver disease, viral hepatitis, and metastasis were analyzed to determine hepatic acid/base status (pH) and to derive absolute molar concentrations of hepatic phosphorus metabolites rather than metabolite ratios. These parameters allow diagnosis and differentiation of several liver pathologies, suggesting an increasing future role of MRS in medical investigation, clinical diagnosis, and patient treatment.

Adenosine Triphosphate↗

PubMed1989

Response of tumors to therapy studied by 31P magnetic resonance spectroscopy.

Magnetic resonance (MR) methods have been used to study the metabolic and vascular response of model tumors to tumor necrosis factor (TNF). Magnetic resonance measurements demonstrated acute reductions in tumor blood flow, measured from tumor uptake of D2O, and in tumor adenosine triphosphate (ATP), measured by 31P magnetic resonance spectroscopy (MRS) following administration of TNF. The decrease in ATP generally followed reduction in tumor blood flow, and therefore was probably due to ischemia caused by damage to tumor vasculature. Superficial human tumors have been studied by MRS to characterize their 31P spectra, and to measure metabolic changes during therapy. The ratio of the intensities of the phosphomonoester (PME) and ATP resonances (PME/ATP) was much higher in tumors than in the normal tissue displaced by the tumors. During therapy, decreases in PME/ATP were detected that paralleled, but did not anticipate, decreases in tumor size. In some cases, a transient increase in PME/ATP was detected during therapy, which did not correlate with changes in tumor size, and which may reflect stimulation of cell growth in some tumor zones.

Adenosine Triphosphate↗

PubMed1989

Alcoholic liver disease: quantitative image-guided P-31 MR spectroscopy.

Phosphorus-31 magnetic resonance (MR) spectroscopy was performed on the liver of patients with alcoholic hepatitis (n = 10), alcoholic cirrhosis (n = 9), and viral hepatitis B (n = 3) and on healthy control subjects (n = 21). A hydrogen-1 MR image-guided localization technique (ISIS) was used to acquire P-31 spectra selectively from a volume of interest within the liver. Spectra were analyzed to yield absolute molar concentrations of hepatic phosphomonoesters, phosphodiesters, inorganic phosphate, and adenosine triphosphate. It was found that (a) hepatic metabolite ratios in alcoholic liver disease were not significantly different from those in healthy subjects, (b) absolute hepatic metabolite concentrations were decreased by 25%-46% in alcoholic hepatitis and 13%-50% in alcoholic cirrhosis compared with those in healthy subjects, and (c) hepatic intracellular pH was 7.4 in healthy subjects, more acidic in alcoholic cirrhosis, and more alkaline in alcoholic hepatitis. The findings indicate that hepatic metabolite ratios are not a sensitive measure of alcoholic liver disease, that quantitative P-31 MR spectroscopy is able to noninvasively show metabolic changes associated with alcoholic liver disease, and that alcoholic hepatitis and cirrhosis may be distinguished by means of hepatic intracellular pH measured with MR spectroscopy.

Adenosine Triphosphate↗

PubMedDate not supplied

Use of computer simulations for quantitation of 31P ISIS MRS results.

The difficulties in quantitation of in vivo 31P spectra are exacerbated by the fact that, in general, coils with inhomogeneous B1 fields are used with in vivo samples. A general method for quantitation of in vivo 31P MRS results obtained with the ISIS localization method was developed using computer simulations. The simulation calculates the preparation of the sample magnetization throughout the sample by the ISIS pulse sequence, as well as the sensitivity of signal reception. The calculation accounts for both the B1 field and the B0 gradients applied to the sample. The sensitivity of the experiment is expressed by integration of the simulated signal over the sample, assuming a homogeneous sample. The primary advantage of this approach is that a separate localization experiment on a phantom of known concentration is not required each time parameters of the localization experiment, such as dimensions or location of the localized volume, are altered. In addition, the simulations indicate the degree of contamination (signal from outside of the localized volume) that occurs, and provide a means of comparing different executions of the ISIS experiment. Experiments were performed on phantoms to verify the simulations, and experimental results on human brain and liver are reproduced to show that this approach provides reasonable estimates of metabolite levels in terms of molar concentrations.

Computer Simulation↗

PubMedDate not supplied

Effects of brain membranes on 1H nuclear magnetic resonance signal intensity of ethanol in vitro.

In vivo proton nuclear magnetic resonance (1H NMR) studies of ethanol in animal and human brains have shown that only a fraction of ethanol in brain is visible by NMR. The goals of these in vitro 1H NMR experiments were to determine: (1) whether the interaction of ethanol with brain membranes in vitro diminishes ethanol visibility; and (2) if a magnetization transfer (MT) effect can be observed for the interaction of ethanol with brain membranes in vitro. Furthermore, pilot studies were performed to determine if the brain membranes from rats chronically exposed to ethanol had a different effect on ethanol NMR visibility and spin-spin relaxation time (T2) than brain membranes obtained from control rats. Results show that the NMR visibility of ethanol is lower in rat brain membrane suspensions in vitro as compared to ethanol in saline solutions. The factors decreasing ethanol NMR visibility are T2 relaxation, water presaturation time, and off-resonance saturation by a frequency-dependent MT pulse. One-pulse NMR measurements without water presaturation showed that ethanol visibility was significantly increased by 15% in brain membrane suspensions of ethanol-fed rats, suggestive of decreased ethanol partitioning compared to controls. Furthermore ethanol in brain membrane suspensions from ethanol-fed rats showed smaller MT effects than from control rats. These results provide a mechanism for decreased NMR visibility of ethanol in brain, and suggest that chronic exposure to ethanol produces membrane changes which result in increased NMR visibility.

Animals↗