Localization of radiolabeled monoclonal antibody in a human soft tissue sarcoma xenograft.

125I-labeled monoclonal antibody 19-24 (mouse isotype IgG1) was evaluated for its potential usefulness in the clinical radioimmunodetection of sarcoma. The antibody reacts with a cell surface antigen preferentially expressed in many human soft tissue and bone sarcomas. Chromatographic and electrophoretic analyses indicated that the labeled preparation was relatively pure. Binding studies in vitro demonstrated that specificity for antigen was retained after iodination and indicated that the labeled antibody possessed an immunoreactivity in excess of 90% and a binding constant of 8.1 X 10(9) M-1. When administered to athymic NCr-nu/nu mice bearing 1-cm diameter human fibrosarcoma HT-1080 xenografts, the labeled antibody preferentially localized in tumor deposits. Maximum tumor-to-blood radioactivity ratios (2.2-3.4) were obtained 7 days after antibody injection. Specificity of the localization was confirmed with a control mouse IgG1 antibody and by using a nonreactive xenograft. Distinct tumor images were obtained by gamma camera without the use of subtraction techniques, demonstrating the possible clinical utility of the labeled antibody.

Rapid miniaturized chromatographic quality-control procedures for Tc-99m radiopharmaceuticals.

Our laboratory has adopted a complete miniaturized charomatography system for Tc-99m radiopharmaceuticals in order to improve upon the commercial systems currently available. Three distinct, separate, chromatographic procedures are used to determine the labeling efficiencies of Tc-99m-labeled sulfur colloid, MAA, stannous chloride, phytate, DMSA, DTPA, pyrophosphate, diphosphonate, methylene diphosphonate, polyphosphate, and glucoheptonate. The chromatographic systems include Whatman 31 ET paper and acetone, Gelman ITLC-SG and 0.9% sodium chloride, and Gelman ITLC-SA and acetone. The chromatographic strips are miniaturized (1 X 6 cm), colored-coded, marked, and numbered. All the chromatographic quality-control procedures are simple, rapid, and can easily be incorporated into the routine quality-control program of any nuclear medicine facility.

Improved computer definition of regions of interest by using a double-cursor method.

In the computer analysis of radionuclide studies it is often necessary to define a region of interest (ROI) over an organ or part of an organ. The entire organ boundary is not always apparent on a single image. A method for combining the information from two images in entering the ROI has been developed. It is based on the use of a double cursor that moves simultaneously over both images. Programming was done using special FORTRAN-callable subroutines existing in our system for access to the display. The method is now in routine use for the definition of the left-ventricular ROI during processing of radionuclide cardiac studies.

In vivo labeling of red blood cells with 99mTc: a new approach to blood pool visualization.

A simple and rapid procedure for in vivo labeling of red blood cells (RBC) is presented. The labeling is done with two consecutive intravenous injections, first of "cold" stannous pyrophosphate (Sn-PYP) and then of 99mTc-pertechnetate. Experimentally, a lag time of 30 min between the two injections was found to result in a mean RBC labeling of greater than 95% during the first hour after pertechnetate injection. A total of 75 patients have been explored by scintillation camera imaging of brain, heart, great vessels, aortic bifurcation, testicles, and lower extremities using the technique outlined. High-quality images were obtained.

The effects of inadvertent administration of antineoplastic agents prior to Ga-67 injection: concise communication.

Alteration of the gallium-67 (Ga-67) distribution after administration of chemotherapeutic agents has been demonstrated in experiments on both normal and tumor-bearing animals. We have encountered eight patients who had Ga-67 scintigrams in which the findings were similar to those in the animals experiments: markedly increased uptake in bone, with suppressed uptake in liver, muscle, and tumor. Five of the patients had hematologic neoplasms, and three had solid tumors, and each had received one or more chemotherapeutic agents during the 24 hr preceding Ga-67 administration. In three patients while not on antineoplastic medication subsequent Ga-67 images showed a return to the usual Ga-67 distribution pattern. The altered Ga-67 distribution may result from inhibition of protein synthesis or of a serum-binding agent for Ga-67, or from competitive blockage of specific Ga-67 organ receptors by the antineoplastic agents.

Noninvasive experimental determination of the individual kidney filtration fraction by means of a dual-tracer technique.

A noninvasive method for measurement of the individual kidney filtration fraction (FF) is presented, based on an analysis of the early rise of the kidneys' time-activity curves obtained after simultaneous injection of tubular [131I] ortho-iodohippurate and glomerular (Tc-99m DTPA) tracers. The analysis is based on the assumption that an insignificant amount of tracer leaves the kidney during the first few moments following injection. Therefore the kidney activity during this period is directly proportional to the integral of the blood (heart) activity. The dual-tracer technique allows the direct calculation of the ratio of glomerular to tubular clearances, i.e., the FF. In vivo studies were performed on 12 dogs, including normals as well as others with acute ureteral ligation or Benemid-induced tubular blockade. The calculated FF correlated well with the FF obtained from single-shot clearances performed simultaneously. We conclude that the FF can be calculated directly for each kidney, noninvasively, from the early part of the tubular and glomerular time-activity curves by noninvasive external detection.

Equilibrium radionuclide gated angiography in patients with tricuspid regurgitation.

Equilibrium gated radionuclide angiography was performed in 2 control groups (15 patients with no organic heart disease and 24 patients with organic heart disease but without right- or left-sided valvular regurgitation) and in 9 patients with clinical tricuspid regurgitation. The regurgitant index, or ratio of left to right ventricular stroke counts, was significantly lower in patients with tricuspid regurgitation than in either control group (range and mean +/- standard error of the mean 0.4 to 1.0, 0.7 +/- 0.1 versus 1.0 to 1.5, 1.3 +/- 0.1 and 1.0 to 2.9, 1.5 +/- 0.1, respectively, p less than 0.001). Time-activity variation over the liver was used to compute a hepatic expansion fraction which was significantly higher in patients with tricuspid regurgitation than in either control group (1.4 to 11.4, 5.8 +/- 1.0% versus 0.6 to 3.4, 1.9 +/- 0.3% and 1.0 to 5.1, 2.3 +/- 0.2%, respectively, p less than 0.001). Fourier analysis of time-activity variation in each pixel was used to generate amplitude and phase images. Only pixels with values for amplitude at least 7% of the maximum in the image were retained in the final display. All patients with tricuspid regurgitation had greater than 100 pixels over the liver automatically retained by the computer. These pixels were of phase comparable to that of the right atrium and approximately 180 degrees out of phase with the right ventricle. In contrast, no patient with no organic heart disease and only 1 of 24 patients with organic heart disease had any pixels retained by the computer. In conclusion, patients with tricuspid regurgitation were characterized on equilibrium gated angiography by an abnormally low regurgitant index (7 of 9 patients) reflecting increased right ventricular stroke volume, increased hepatic expansion fraction (7 of 9 patients), and increased amplitude of count variation over the liver in phase with the right atrium (9 of 9 patients).

Computer processed 99mTc-DTPA studies of renal allotransplants.

In order to refine the diagnostic possibilities of the radionuclide renal study in transplanted patients and to compensate for the nonspecificity of the 131I-hippuran study in some situation, 99mTc-DTPA WAS USED SIMULTANEOUSLY FOR IMAGING AND TIME-ACTIVITY CURVES. For these curves to be significant, appropriate background subtraction had to be made with a simple computer-processing method. The results obtained have shown that it is possible to distinguish marked acute tubular necrosis from milder degrees, thus affording a prognostic index in the immediate postoperative period, when the hippuran data are often nonspecific. Further, the diagnosis and follow-up of acute rejection episodes can be improved by the DTPA processed curves. Although these curves when examined individually do not show a specific pattern for rejection, they may reveal striking evolutionary changes when compared to the previous studies, even when the hippuran curves are unchanged. The physiologic basis for the differences between the two time-activity curves may be related to the differential handling of the two radiopharmaceuticals by the kidney.

Partial splenic embolization, an alternative to splenectomy--results of a prospective, randomized study.

UNLABELLED: We conducted a prospective, randomized study comparing transcatheter partial splenic embolization (PSE) with splenectomy (SX) in 53 renal transplant candidates. An additional 112 PSE procedures were performed for various indications in 101 patients. STUDY RESULTS: A mean +/- SD of 65% +/- 16% of splenic mass was ablated in the PSE group. The early postoperative morbidity rate was similar in the two study groups, as was the duration of hospital stay. Abscess or rupture of the spleen were not encountered. Severe pancreatitis occurred only in the SX group. Renal transplantation was carried out in equivalent numbers in both groups, with a similar long-term (2.5 to 4.0 years) graft survival (60% versus 66%). No difference in long-term patient mortality was noted. Splenic "regeneration" occurred frequently after PSE. PSE experience exclusive of study: Embolization attempts failed in nine patients. Repeat PSE was performed in 11 of the 101 patients. Where hypersplenism was the primary indication, PSE resulted in significant improvement in the hematologic parameters. The incidence of serious complications was acceptably low. There were two late procedure-related deaths. Our conclusion from the study and the total experience of 137 PSE procedures is that PSE offers an acceptably safe alternative to SX in selected high-risk patients in whom both the surgical intervention and the resulting asplenic state carry a prohibitive risk.

Chronic hypoxemia depresses global ventricular function and predisposes to the depletion of high-energy phosphates during cardioplegic arrest: implications for surgical repair of cyanotic congenital heart defects.

Persistence of impaired ventricular function after repair of cyanotic congenital heart defects may be due to previous exposure to chronic hypoxemia or to perioperative ischemic injury. Clarification of this phenomenon was sought in a canine model of cyanotic cardiovascular disease (Group I), in which the left atrium was anastomosed proximal to the banded pulmonary artery. Animals that had pulmonary artery banding alone (Group II) or no prior surgical intervention (Group III) served as controls. All Group I animals became cyanotic during the study period (arterial oxygen tension, 38 +/- 4 mm Hg; hematocrit, 55 +/- 5%). Radionuclide-determined ejection fractions performed three months after operation showed significant depression of global biventricular function by 16 to 29% (p less than 0.05) compared with groups II and III. On cardiopulmonary bypass, all hearts were subjected to 4 degrees C potassium cardioplegic arrest and reperfusion with serial assays for myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels. The ATP and CP stores in each ventricle were similar at all sampling intervals, and preischemic levels were comparable in cyanotic and control groups. However, ATP levels were significantly depressed 37 to 43% from preischemic levels (p less than 0.02) after arrest and reperfusion in cyanotic dogs, but they were preserved in Groups II and III. During ischemia, CP stores were depleted to 27% of preischemic values in Group I but only to 46 to 63% of preischemic levels in the control groups (p less than 0.05). These data indicate that chronic hypoxemia impairs global ventricular function and predisposes to the accelerated depletion of high-energy phosphates during cardioplegic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide synthetic Fourier images of cardiac wall motion abnormalities.

At present, the phase images together with amplitude images are used in nuclear medicine to aid the diagnosis of cardiac regional wall motion abnormalities (RWMA). The phase images represent the spatial distribution of the relative phase of the first harmonic fit of pixel time activity curves, and the amplitude images represent the distribution of the amplitude of the fit. These images contain only part of the information present in the original radionuclide images, and have to be mentally integrated with other known information to obtain a diagnosis. The proposed synthetic Fourier images overcome these deficiencies as their pixel intensity is a function of additional Fourier parameters of pixel time activity curves and of pixel location and are not limited to the first harmonic. But most importantly, their computation is based on "teaching" the computer by examples of previously diagnosed cases. The images offer direct and robust diagnosis which is superior to that derived from separate phase and amplitude images, especially for the detection of mild RWMA.

The accuracy of SPECT brain activation images: propagation of registration errors.

Functional single photon emission computed tomography (SPECT) images of brain activation are based on a comparison of base line and activation images. The correctness of the functional images depends, among other factors, on the accurate spatial registration (alignment) of the base line and activation image data. The relationship between the registration errors and the errors of the resulting functional images is studied. It is shown that misregistration errors as small as a shift by 1/8 pixel or rotation by 1 degree result in 5%-10% errors of the pixel values of functional SPECT images of regional blood flow (the ratio and the relative difference images).

The accuracy of SPECT brain activation images: propagation of registration errors.

Functional single photon emission computed tomography (SPECT) images of brain activation are based on a comparison of base line and activation images. The correctness of the functional images depends, among other factors, on the accurate spatial registration (alignment) of the base line and activation image data. The relationship between the registration errors and the errors of the resulting functional images is studied. It is shown that misregistration errors as small as a shift by 1/8 pixel or rotation by 1 degree result in 5%-10% errors of the pixel values of functional SPECT images of regional blood flow (the ratio and the relative difference images).

Postoperative cognitive and single photon emission computed tomography assessment of patients with resection of perioperative high-risk arteriovenous malformations.

We studied the outcome of 10 patients who had undergone high-risk surgery for an arteriovenous malformation at our institution between November 1991 and November 1993. All of the lesions were located in the dominant (left) hemisphere. Perioperative risk was assessed by the location of the lesion in functionally eloquent cortex (seven patients) or deep structures (two patients) or the lesion's large volume (two patients). Our patients included six women and four men, and their ages ranged from 22 to 53 years (mean, 35.8). Our follow-up study included the evaluation of neurological sequelae but mainly emphasized the study of cognitive deficits (seven major functional clusters), the incidence of depression and behavioral changes, and the assessment of regional cerebral blood flow with single photon emission computed tomography. Six patients returned to a seemingly "normal" daily life with some minor deficits postoperatively, three developed contralateral hemiparesis, and one had disabling cognitive deficits. Our comprehensive cognitive assessment, in particular, showed that although patients might appear "normal" on a routine neurological examination, most patients showed a mild deficit in at least one cognitive function and three were severely impaired. In addition, the single photon emission computed tomographic studies pointed out hypoperfusion in more extensive regions than the surgical defects shown by magnetic resonance imaging or computed tomographic studies. These single photon emission computed tomography images helped to explain some of the cognitive and behavioral changes better than the anatomic studies. This information will make it possible for the physician to offer continuing supportive care for the patient in postoperative transition to normal life activities.

Fourier classification images in cardiac nuclear medicine.

At present, the diagnosis of cardiac left ventricular regional wall motion abnormalities (RWMA) in nuclear medicine is aided mainly by phase images and amplitude images, which picture the spatial distribution of the phase and of the amplitude of the first harmonics of pixel time activity curves, respectively. However, they do not utilize other information contained in the original radionuclide images, and they do not offer a direct diagnostic interpretation of the data. The proposed Fourier classification images (FCI) overcome these deficiencies. Their pixel intensities express directly the diagnostic class of RWMA. The FCI pixel intensities are functions of pixel coordinates, Fourier features of pixel time activity curves, and their distribution parameters, and they are not limited by the first harmonics model. The derivation of the pixel classifier includes normalization transformation of coordinates and activities. Fourier analysis of raw image data, and teaching the computer by examples of already diagnosed cases with the help of discriminant analysis. FCI offer direct and robust diagnosis of RWMA, superior to that derived from phase and amplitude images, especially in the detection of mild RWMA.

Pitfalls in diagnosing brain death in infancy.

A 3-year-old child with phenotypic trisomy 18 syndrome survived 26 days after a cardiopulmonary arrest, secondary to an acute viral illness. The child was deeply comatose. No barbiturates, other sedatives, or aminoglycoside antibiotics had been recently administered. The child was normothermic with adequate cardiovascular function. Brain stem function was absent, as assessed by testing of brain stem reflexes. Serial cerebral radionuclide angiograms (CRAG) documented intact cerebral blood flow while electrocerebral silence (ECS) was present on two consecutive EEG recordings within 24 hours. Preservation of intracranial circulation was confirmed by rapid rotational computed tomographic (CT) scans. Cranial CT scans also revealed communicating hydrocephalus, and bilateral basal ganglia hemorrhages. This unusual case illustrates discordance between apparent irreversible loss of cortical function as indicated by electrocerebral silence with preserved cerebral blood flow. The implications of these apparent paradoxical events will be discussed in the context of defining brain death in children.

Technical parameters of in vivo red blood cell labeling with Technetium-99m.

The in vivo labeling of red blood cells (RBC) using sequential injections of stannous pyrophosphate and 99mTc-pertechnetate has resulted in excellent blood pool images since it was initiated in our laboratory in 1975. Recently certain technical parameters of the procedure have been further researched and clarified. The optimum RBC labeling has been obtained by using 1.43 mg "cold" Sn-PYP/1000 ml blood and a 30-minute lag time prior to pertechnetate injection (15-20 mCi). The binding of 99mTc to RBCs is not instantaneous, but requires several minutes for completion. The "secondary" RBC labeling effect of additional pertechnetate, added after the initial in vivo labeling, demonstrates an initial rapid fall in the labeling efficiency as a function of time followed by a more gradual decrease; the level of baseline (spontaneous) RBC labeling is achieved approximately 8 days after an initial in vivo labeling. Monitoring in vivo RBC labeling over several hours indicates that more than 90% of the initial activity was still in the vascular blood pool at 4 hours, bound to RBCs.

Positive captopril renal scintigraphy in a patient with extensive bilateral renal interlobar arterial disease.

The authors determined an unusual cause of renovascular hypertension in a 29-year-old man with the recent onset of hypertension and a history of intravenous substance abuse. Captopril renal scintigraphy (CRS) demonstrated bilateral renogram changes and a decrease in estimated global glomerular filtration rate. The abdominal aortogram failed to show renal artery or branch artery stenosis. Magnified selective views of the kidneys demonstrated extensive, bilateral, small vessel interlobar disease. Two major points are illustrated in this patient. First, in the presence of positive CRS results and a history of renovascular hypertension, bilateral, selective, magnified renal angiography should be performed in accordance with standard abdominal aortic views when large vessel disease is not detected. Second, although surgical intervention is not an option in such patients, finding the cause of hypertension is important for patient management.

Incidence and consequences of breast artifacts in radionuclide cardiac studies.

A retrospective evaluation was done on 426 radionuclide cardiac studies performed on female patients at our institution from January through September, 1980. These procedures included pyrophosphate (PYP) myocardial scans, resting and exercise Tl-201 studies, and gated equilibrium studies. The purpose of this evaluation was to document the incidence and possible consequences of breast artifacts in various cardiac procedures. We found the incidence to range from 30 to 50% of the studies performed, and both the incidence and type of artifact encountered varied with the type of procedure performed. Furthermore, 13 to 35% of patients had artifacts directly overlying the myocardium. The possible consequences, including potential misdiagnosis, interference with computer derived quantitative parameters, and the technical maneuvers necessary to avoid or alleviate these problems are discussed.

Visualization of atrial myocardium with Tl-201: case report.

A case of right atrial visualization on Tl-201 imaging in a patient with marked right atrial enlargement secondary to atrial septal defect is described. The misinterpretation of Tl-201 an gated cardiac studies on initial inspection, due to this unusual finding, and the importance of obtaining special lateral and oblique view for correct identification of cardiac chambers are discussed.