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Biomedical subjects

W L Rogers

Publications and source records attributed to W L Rogers.

At least 19 recordsLinked to original sources
PubMed1992

Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.

The depressor, natriuretic and cyclic GMP responses to several species of brain natriuretic peptide (BNP) were compared to atrial natriuretic peptide (ANP) 99-126 in conscious spontaneously hypertensive rats (SHR) and in conscious cynomolgus monkeys treated with vehicle or the selective neutral endopeptidase (NEP 3.4.24.11) inhibitor N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta- alanine (SQ 28,603). In the conscious SHR, the natriuretic and cyclic GMP responses to 3 nmol/kg i.v. rat BNP-32 greater than rat ANP 99-126 greater than pig BNP-26 and were significantly potentiated by 100 mumol/kg i.v. SQ 28,603. Human BNP-32 was inactive in the SHR treated with either vehicle or SQ 28,603. In contrast, 1 nmol/kg i.v. of human BNP-32 stimulated renal and depressor responses in the conscious monkeys that were greater than or equal to those elicited by human ANP 99-126, whereas 3 nmol/kg i.v. rat BNP-32 reduced mean arterial pressure without affecting renal function. Furthermore, SQ 28,603 (100 mumol/kg, i.v.) significantly enhanced the cumulative losses of sodium and cyclic GMP stimulated by each of these peptides. In conclusion, the renal and depressor activities of BNP are highly species specific and are significantly potentiated by an inhibitor of NEP 3.4.24.11 in conscious SHR and monkeys. Therefore, protection of endogenous BNP may contribute importantly to the activity of NEP 3.4.24.11 inhibitors in cardiorenal disorders such as hypertension and congestive heart failure.

Alanine↗
PubMed1992

Technetium-99m-N1-(2-mercapto-2-methylpropyl)-N2-(2-propargylthio-2- methylpropyl)-1,2-benzenediamine (T691): preclinical studies of a potential new tracer of regional cerebral perfusion.

We report in vitro and in vivo preclinical studies of a new cerebral blood flow tracer, [99mTc]N1-(2-mercapto-2-methyl-propyl)-N2-(2- propargylthio-2-methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in vitro chemical stability and accumulates regionally in the brain in a pattern consistent with that of cerebral blood flow. First-pass cerebral extraction determined with the use of the brain uptake index method in the rat was 0.76. Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68% and prolonged retention of 67% of the initially extracted activity. Autoradiographic studies in rats revealed a pattern characteristic of cerebral blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic imaging following systemic injection in the monkey revealed peak brain activity 1 to 2 min postinjection, without significant decline over 60 min. Chromatographic studies of brain as long as 60 min following systemic injection of [99mTc]T691 showed no evidence of tracer metabolism to account for its retention. Overall, [99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral perfusion.

Animals↗
PubMed1991

Testing of local gamma-ray scatter fractions determined by spectral fitting.

The spectral-fitting method of correction for gamma-ray Compton scattering within objects separates the unscattered and scattered components of locally measured energy spectra. Here, we employ a third-order polynomial for the scattering and an approximately constant fitting window. A scatter fraction, defined as total scattered over total unscattered counts within a 20% window, is calculated for each point in our Anger camera images. These scatter fractions are tested against those from Monte-Carlo simulation for 99mTc and against results from semiconductor detector measurements for 131I. A radioactive sphere at several locations within a non-radioactive cylinder and the inverse are imaged for the testing. For one case, reproducibility of the spectral-fitting scatter fraction as a function of the number of unscattered counts within the 20% acceptance window was also determined. With 99mTc, for all cases, the agreement between spectral fitting and the standard estimation method is within 16%. With 131I, for the 'hot' sphere at two locations, the agreement is within 21%. For the 'hot' sphere at the third location (off the cylinder axis towards the camera), the dependence of scatter fraction on transverse distance is good although the absolute values are too large. Scatter fraction reproducibility is within 10% for 1000 or more counts. Therefore, further testing of spectral fitting and initial application to realistic clinical images seem to be in order.

Gamma Cameras↗
PubMed1991

Antihypertensive and renal activity of SQ 28,603, an inhibitor of neutral endopeptidase.

SQ 28,603 is a potent and selective inhibitor of neutral endopeptidase 3.4.24.11 (NEP), an enzyme that degrades atrial natriuretic peptide (ANP). In conscious deoxycorticosterone acetate (DOCA)/salt hypertensive rats, 300 mumol/kg, i.v., of SQ 28,603 significantly lowered mean arterial pressure (MAP) from 177 +/- 12 to 154 +/- 8 mm Hg and increased urinary cyclic guanosine monophosphate (GMP) excretion from 204 +/- 70 to 1,068 +/- 326 pmol/kg/min within 2 h. Urinary sodium excretion increased within 20 min from a control 51.2 +/- 17.3 to 102.1 +/- 26.7 muEq/kg/min. Infusion of SQ 28,603 (3.7 mumol/kg/min) for 6 h in a separate group of conscious DOCA/salt hypertensive rats gradually reduced MAP from 180 +/- 7 to 142 +/- 7 mm Hg and increased urinary cyclic GMP excretion from 182 +/- 36 pmol/kg/min to 1,009 +/- 394 pmol/kg/min. Despite the continuous infusion of the inhibitor, the natriuretic response peaked during the first hour of treatment at 128 +/- 18 muEq/kg/min (vehicle = 54 +/- 10 muEq/min). Plasma ANP was significantly greater in the rats infused with SQ 28,603 than in those receiving vehicle (333 +/- 108 and 98 +/- 14 fmol/ml, respectively). SQ 28,603 also significantly reduced NEP activity by 95% in the kidneys (1.28 +/- 0.08 vs. 18.35 +/- 0.61 mumol/min after SQ 28,603 and vehicle respectively) and by 77% in the lungs (0.29 +/- 0.03 vs. 0.92 +/- 0.14 mumol/kg after SQ 28,603 and vehicle, respectively). In conclusion, inhibition of NEP activity by SQ 28,603 significantly decreased MAP and increased plasma ANP concentrations and urinary excretion of cyclic GMP in conscious DOCA/salt hypertensive rats.

Alanine↗
PubMed1991

Heart failure augments the cardiovascular and renal effects of neutral endopeptidase inhibition in rats.

We compared the cardiovascular and renal actions of the neutral endopeptidase (NEP) inhibitor, SQ 28,603, in normal rats and in rats with healed myocardial infarcts. The infarcted rats were studied in the conscious state 8 weeks after ligation of the left main coronary artery and 4 h after placement of cardiovascular and renal catheters. Infarct size was 39 +/- 1.2% of left ventricle circumference; right ventricle and lung weight to body weight ratios were twice those of normal rats. These postmortem values were shown to be associated with elevated left ventricular end diastolic pressure and high plasma atrial natriuretic peptide (ANP) concentration in separate groups of rats. SQ 28,603 at 100 mumol/kg intravenously (i.v.) caused urine volume and sodium excretion to increase by 79 +/- 11 microliters/min and 8.2 +/- 1.4 microEq/min, respectively, 20 min after injection in infarcted rats; these changes were significantly greater than those in normal rats (12 +/- 5 microliters/min and 1.6 microEq/min, respectively). Thoracic venous pressure decreased by 1.9 +/- 0.4 mm Hg 80 min after SQ 28,603 in infarcted rats and by only 0.1 +/- 0.1 mm Hg in normal rats (p less than 0.05 vs. infarcted rats). SQ 28,603 had no effects on mean arterial pressure (MAP), cardiac output (CO), or glomerular filtration rate (GFR). The observation that NEP inhibition has more pronounced effects in animals with high ambient ANP level than in those with normal ANP is consistent with previous studies in a variety of animal models and supports the concept that NEP inhibition potentiates endogenous ANP.

Alanine↗
PubMed1991

Evaluation of SQ 28,603, an inhibitor of neutral endopeptidase, in conscious monkeys.

The potent neutral endopeptidase inhibitor SQ 28,603 (N-(2-(mercaptomethyl)-1-oxo-3-phenylpropyl)-beta-alanine) significantly increased excretion of sodium from 4.9 +/- 2.3 to 14.3 +/- 2.1 muequiv./min and cyclic 3',5'-guanosine monophosphate from 118 +/- 13 to 179 +/- 18 pmol/min after intravenous administration of 300 mumol/kg (approximately 80 mg/kg) in conscious female cynomolgus monkeys. SQ 28,603 did not change blood pressure or plasma atrial natriuretic peptide concentrations in the normal monkeys. In contrast, 1-h infusions of 3, 10, or 30 pmol.kg-1.min-1 of human atrial natriuretic peptide lowered blood pressure by -3 +/- 4, -9 +/- 4, and -27 +/- 3 mmHg (1 mmHg = 133.322 Pa), increased cyclic guanosine monophosphate excretion from 78 +/- 11 to 90 +/- 6, 216 +/- 33, and 531 +/- 41 pmol/min, and raised plasma atrial natriuretic peptide from 7.2 +/- 0.7 to 21 +/- 4, 62 +/- 12, and 192 +/- 35 fmol/mL without affecting sodium excretion. In monkeys receiving 10 pmol.kg-1.min-1 of atrial natriuretic peptide, 300 mumol/kg of SQ 28,603 reduced mean arterial pressure by -13 +/- 5 mmHg and increased sodium excretion from 6.6 +/- 3.2 to 31.3 +/- 6.0 muequiv./min, cyclic guanosine monophosphate excretion from 342 +/- 68 to 1144 +/- 418 pmol/min, and plasma atrial natriuretic peptide from 124 +/- 8 to 262 +/- 52 fmol/mL. In conclusion, SQ 28,603 stimulated renal excretory function in conscious monkeys, presumably by preventing the degradation of atrial natriuretic peptide by neutral endopeptidase.

Alanine↗
PubMed1991

Clinical SPRINT imaging. Preliminary results compared to conventional SPECT brain scanning using Tc-99m HMPAO.

We have performed initial clinical studies using the high resolution single photon ring tomograph (SPRINT) and Tc-99m HMPAO. To determine what additional anatomic detail can be depicted using this high resolution, dedicated head, multidetector SPECT device compared to conventional SPECT, six patients with stroke and one normal volunteer were imaged after the injection of 20 mCi Tc-99m HMPAO on a conventional rotating Anger gamma camera (GE-400AC), followed immediately by imaging on SPRINT. Imaging acquisition on the GE-400AC gamma camera was performed using 360 degrees rotation, 64 stops, at 30 sec/stop, yielding an average of 985,714 counts for a 10.0 mm thick slice. GE-400AC images were of good quality, having in-plane full width half maximum (FWHM) resolution of approximately 15 mm. SPRINT acquisition of image data was performed using both the high resolution and high sensitivity apertures, with data collection over 15 or 20 minutes of imaging time accumulating approximately 500,000 counts and 1,000,000 counts, respectively, from patients in a 10.0 mm thick slice, achieving an in-plane FWHM resolution of approximately 8 mm and 10 mm for the two apertures, respectively. Both image resolution and contrast for visualization of gray, white, and cerebral spinal fluid filled brain structures were improved using SPRINT compared with the GE-400AC. We conclude that SPRINT is well suited for brain imaging with Tc-99m HMPAO and is of particular value for applications demanding high resolution.

Adult↗
PubMed1990

Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow.

SQ30217 is a new, technetium-99m-(99mTc) labeled perfusion agent introduced for cardiac imaging. To evaluate the myocardial tracer kinetics, 99mTc-SQ30217, was injected intracoronarily in open-chested dogs under baseline conditions and after administration of intravenous (i.v.) dipyridamole. Myocardial first-pass retention fraction averaged 0.90 +/- 0.04. Clearance of the tracer occurred in a biexponential manner. Sixty-seven percent of retained activity cleared with a half-time of 2.3 +/- 0.6 min, while the residual activity demonstrated slow clearance. The clearance rate of the rapid phase correlated with myocardial blood flow (r = 0.72, p less than 0.001). Myocardial SQ30217 clearance rate following i.v. injection as determined by dynamic imaging with tomography (SPRINT) averaged 21 +/- 4 min and increased to 13 +/- 4 min following dipyridamole. Thus, 99mTc-SQ30217 is a promising flow tracer with high initial myocardial retention and rapid tissue clearance, which allow repeated flow determinations within short time intervals using advanced SPECT technology.

Animals↗
PubMed1990

SPECT dual-energy-window Compton correction: scatter multiplier required for quantification.

The dual-energy window Compton-scattering correction technique is defined here especially for accurate quantification of focal regions having higher than average uptake. The quantification is relative to a known-activity reference source. The scatter multiplier ("k" value) is determined for a radioactive 99mTc sphere on or off the axis of a cylinder containing water with or without background. Both maximum likelihood and filtered-backprojection reconstruction are employed. Either projections or tomograms are corrected. With tight regions of interest, there is a tendency for the requisite "k" value to be slightly lower as the diameter of the cylinder is increased. Neither sphere location nor background perturbs "k", however, so a constant value is a good, first approximation. Then a two-sphere validation test yields an accuracy of 8% with subtracted-tomograms ("k" = 1.30) and 2% with subtracted-projections ("k" = 1.20). With a reference-source region of interest which is four times larger, "k" is reduced and also now depends on background. Although equivalent quantitatively, maximum likelihood is preferable to filtered backprojection with Chang attenuation correction since it produces a less-noisy image.

Algorithms↗
PubMed1979

Application of ART to time-coded emission tomography.

Devices for single-photon emission tomography currently take projections either in a plane over a full angular range (0--360 degrees) or in a volume with a limited angular range. The planar, pseudo-random, time-coded aperture, in conjunction with an Anger camera, is a device of the limited angular range type. It employs multiple pinholes whose transmission varies as a function of time. Previously, image reconstruction was accomplished by simple back-projection of coefficients obtained by time-correlating pinhole transmission with detector-element count rate, resulting in a low-contrast image. Using the Algebraic Reconstruction Technique (ART) a method is introduced for division of the correlation coefficients into subsets allowing the three-dimensional reconstruction to be accomplished on a minicomputer. Results from simulations and experimental phantom data show that ART improves depth resolution compared to back-projection, that under-relaxation produces better images in the case of noisy data, and that the division of the correlation coefficients into subsets has no effect on quality. The images depict the expected resolution degradation in the direction normal to the detector plane due to the limited angular range of projections but yield quantitative results whose relative values are good, even though attenuation is neglected.

Mathematics↗
PubMed1979

Exercise radionuclide ventriculography: practical considerations and sensitivity of coronary artery disease detection.

Eighty-nine patients were evaluated for coronary artery disease (CAD) with exercise radionuclide ventriculography (ERV) and contrast coronary angiography. In 70 patients with documented lesions the ERV was abnormal in 65 for a sensitivity of 93%. In patients with normal coronary arteries, the ERV was abnormal in none for a specificity of 100%. Sensitivity of ERV for detecting CAD was affected by the level of exercise achieved. In patients with documented CAD who achieved adequate exercise (i.e., pressure rate product (PRP) greater than 250 or the development of angina or ST segment depression during exercise), the sensitivity was 98% (56 of 57 patients). In those with documented CAD who failed to achieve adequate exercise, the sensitivity was 69% (9 of 13 patients).

Angiography↗
PubMed1979

Thyroid scintigraphy with time-coded aperture.

Coded aperture imaging (CAI) and multiple-view pinhole imaging (MVPI) of the thyroid were compared in 19 patients to determine whether CAI's theoretical advantages of high resolution, high efficiency, freedom from distortion, accurate size representation, and tomographic presentation could be realized in the clinical setting, and to determine whether CAI offers any advantage over conventional MVPI. The coded aperture images were judged better than the pinhole images in five cases, equal in 13 cases, and worse in one case. The major problem with CAI was the long reconstruction time. Further development and an extended clinical trial appear warranted.

Humans↗
PubMed1978

Myocardial imaging using emission computed tomography.

Single-photon emission computed tomography (ECT) was evaluated during myocardial studies in dogs. Acute anterior and posterior infarcts were imaged following injection of 99mTc-pyrophosphate or 201Tl. In most cases, tomographic delineation of infarct location and extent correlated with tissue section. The 99mTc images were far superior to the 201Tl images. ECT improves delineation of tracer within the myocardium.

Animals↗
PubMed1978

Myocardial infarct quantification in the dog by single photon emission computed tomography.

Radionuclide techniques for sizing acute myocardial infarction have been hampered by the intrinsic limitations of the scintillation camera. Emission computed tomography can overcome these limitations. Single photon emission computed tomograms of the distribution of technetium-99m pyrophosphate in acute anterior and posterior infarcts were obtained in 16 dogs after death. Tomograms were also obtained in 10 dogs during life without gating. The size of the infarcts was determined by staining gross sections of the heart with nitro blue tetrazolium, dissecting out the infarcted tissue and weighing it. Infarct sizes were determined from the tomographic images and compared with the measured infarct sizes. Good images showing the location and three-dimensional extent of the infarcts were obtained in all dogs. The measured and calculated infarct sizes correlated well (r = 0.85). Comparison of the calculated sizes in the living (non-gated) and dead ("physiologically" gated) animals showed reasonable agreement (r = 0.87). Single photon emission computed tomography is a feasible and useful technique for localizing and sizing acute myocardial infarctions.

Animals↗
PubMed1978

Clinical comparison of cardiac blood pool visualization with technetium-99m red blood cells labeled in vivo and with technetium-99m human serum albumin.

Technetium-99m red blood cells (Tc-RBC) labeled by an in vivo technique were compared with two preparations of Tc-99m human serum albumin (HSA) for cardiac blood-pool imaging. Relative distribution of the tracers was analyzed on end-diastolic frames of gated blood-pool studies and on whole-body (head to mid-thigh) anterior pinhole images. The Tc-RBC demonstrated greater relative percentage localization in the cardiac blood pool, higher target-to-background ratios in the left ventricle, and less liver concentration. For cardiac blood-pool imaging, Tc-RBC labeled by the in vivo approach appears to be superior to the two Tc-HSA preparations studied.

Cardiac Volume↗
PubMed1977

The Humongotron--a scintillation-camera transaxial tomograph.

An emission transaxial tomographic system using a scintillation camera as the detector is described. The unit allows accurate positioning of a scintillation camera's detector at any angle around a patient in order to obtain the multiple projection images needed for transaxial tomography, and it is capable of imaging any area of the body. The camera can also be used for all types of conventional imaging procedures. Image processing is performed by a small on-line computer. A convolution algorithm and a mathematical technique for approximate absorption correction are used to obtain high-resolution and high-contrast images with good quantitative accuracy. The operation of the system is described and representative phantom and patient studies are presented to illustrate the capabilities of the system.

Brain Neoplasms↗
PubMed1975

Digital tomographic imaging with time-modulated pseudorandom coded aperture and Anger camera.

The properties of a time-modulated pseudorandom coded aperture with digital reconstruction are compared with those of conventional collimators used in gamma-ray imaging. The theory of this coded aperture is given and the signal-to-noise ratio in an element of the reconstructed image is shown to depend on the entire source distribution. Experimental results with a preliminary 4 X 4-cm pseudorandom coded aperture and an Anger camera are presented. These results include phantom and human thyroid images and tomographic images of a rat bone scan. The experimental realization of the theoretical advantages of the time-modulated coded aperture gives reason for continuing the clinical implementation and further development of the method.

Radionuclide Imaging↗