Differentiation of cell-mediated and humoral rejection by orthoiodohippurate kinetics.

The differentiation of two types of renal graft rejection may be made early in incipient stages by means of a comprehensive renal function study. In the acute cell-mediated form, prolongation of orthoiodohippurate renal transit time as reflected in a diminished excretory index (El) is first observed, followed by a diminution in the effective renal plasma flow (ERPF). On reversal of the process, El precedes ERPF in returning to normal. In chronic humoral rejection, the principle feature is simple reduction of ERPF; transit time within the kidney appears normal. No reversal processes have been observed, although the process may be decelerated. At approximately 100 ml/min ERPF, these kidneys may undergo an acceleration of the clinical failure with rapid deterioration in El and in ERPF. At this point, surgical removal of the kidney has been carried out.

Determination of glomerular filtration rate by single-plasma sampling technique following injection of radioiodinated diatrizoate.

Measurement of glomerular filtration rate (GFR) based on the radioactivity concentration in a single-plasma sample obtained after the injection of radioiodinated diatrizoate (DTZ) has been described. Simultaneous determinations of GFR by use of DTZ based on multiple-sample plasma disappearance curves and inulin correlate highly. Certain theoretical volumes of distribution (injection dose counts divided by plasma concentration expressed as counts per liter of plasma) correlate highly with GFR determined by the multiple-sample plasma disappearance curves. For patients with relatively high GFR (greater than 100 ml/min) best correlations were obtained at 120 min; for patients with GFR 60-100 ml/min, best correlations were obtained at sampling times of 150 min after injection and for patients with GFR less than 60 ml/min, the ideal sampling time was 230 min after injection. For general use the 180-min sampling time may suffice. Since the formulae were found to produce nearly identical GFR values for data obtained from the use of diethylenetriaminepentaacetic acid and DTZ, the former radiopharmaceutical can probably be substituted for diatrizoate using these formulae and sampling times as long as absence of plasma protein binding of the labeled chelate can be demonstrated.

In vivo cross-match by chromium-51 urinary excretion from labeled erythrocytes: a case of anti-Gerbich.

We studied a patient with an alloantibody to the high-frequency red blood cell (RBC) antigen Gerbich. A nationwide search for rare Gerbich-negative blood (less than 1:45,000 donors) located only seven units, and our supply was quickly exhausted. By using an in vivo cross-matching method, we demonstrated that this anti-Gerbich did not cause RBC destruction. Regular Gerbich-positive transfusions could then proceed without hemolysis. This cross-match test was based on the determination of the urinary excretion rates of injected radioactive chromium-labeled donor erythrocytes by which it was possible to determine compatibility only 24 hr after the test was begun. The procedure provides an easy and accurate means for in vivo cross-matching of conventionally incompatible donor blood.

Single-sample method for the estimation of glomerular filtration rate in children.

A method for the determination of the glomerular filtration rate (GFR) in children which involves the use of a single-plasma sample (SPS) after the injection of a radioactive indicator such as radioiodine labeled diatrizoate (Hypaque) has been developed. This is analogous to previously published SPS techniques of effective renal plasma flow (ERPF) in adults and children and GFR SPS techniques in adults. As a reference standard, GFR has been calculated from compartment analysis of injected radiopharmaceuticals (Sapirstein Method). Theoretical volumes of distribution were calculated at various times after injection (Vt) by dividing the total injected counts (I) by the plasma concentration (Ct) expressed in liters, determined by counting an aliquot of plasma in a well type scintillation counter. Errors of predicting GFR from the various Vt values were determined as the standard error of estimate (Sy.x) in ml/min. They were found to be relatively high early after injection and to fall to a nadir of 3.9 ml/min at 91 min. The Sy.x Vt relationship was examined in linear, quadratic, and exponential form, but the simpler linear relationship was found to yield the lowest error. Other data calculated from the compartment analysis of the reference plasma disappearance curves are presented, but at this time have apparently little clinical relevance.

Thallium-201/technetium-99m-phytate (colloid) subtraction imaging of hepatocellular carcinoma.

UNLABELLED: This paper evaluates the clinical usefulness of 201Tl to image hepatocellular carcinoma (HCC), using 201Tl, 99mTc-phytate (colloid) and a three-headed SPECT camera. METHODS: The tumor-to-nontumor ratios (T/N) of 201Tl for different categories of HCC were generated. Tumors were emphasized by image subtraction (201Tl-99mTc-colloid). Thirty-three lesions in 16 patients (18 studies) with HCC were evaluated. There were 19 untreated nodular, five untreated diffuse, five local recurrent and four necrotic lesions after interventional therapy. RESULTS: The mean T/N were as follows: untreated nodular 1.54 +/- 0.31 (mean +/- s.d.), untreated diffuse 1.28 +/- 0.26, local recurrence 1.50 +/- 0.29 and necrosis 0.22 +/- 0.06. All the tumors (except necrotic areas) were enhanced by the image subtraction. CONCLUSION: Thallium-201 is useful for liver tumor imaging but 99mTc-phytate (colloid) is essential to discriminate 201Tl tumor uptake from normal liver accumulation. Image subtraction (201Tl/99mTc-colloid) is helpful in detecting HCC.

Assessment of systolic thickening with thallium-201 ECG-gated single-photon emission computed tomography: a parameter for local left ventricular function.

We measured left ventricular (LV) systolic thickening expressed as a systolic thickening ratio in 28 patients, using 201Tl ECG-gated SPECT. Five normals, 15 patients with prior myocardial infarction, 5 with hypertrophic cardiomyopathy, and 3 with dilated cardiomyopathy were studied. The systolic thickening ratio was calculated as [(end-systolic--end-diastolic pixel counts) divided by end-diastolic pixel counts], using the circumferential profile technique of both end-diastolic and end-systolic short axial images. Functional images of the systolic thickening ratio were also displayed with the "bull's-eye" method. The mean systolic thickening ratio thus calculated were as follows: normals, 0.53 +/- 0.05 (mean +/- 1 s.d.); non-transmural prior myocardial infarction, 0.33 +/- 0.09; transmural prior myocardial infarction, 0.14 +/- 0.05; hypertrophic cardiomyopathy in relatively nonhypertrophied areas, 0.56 +/- 0.11; hypertrophic cardiomyopathy in hypertrophied areas, 0.23 +/- 0.07; and dilated cardiomyopathy, 0.19 +/- 0.02. The systolic thickening ratio analysis by gated thallium SPECT offers a unique approach for assessing LV function.

Assessment of left ventricular volume using ECG-gated SPECT with technetium-99m-MIBI and technetium-99m-tetrofosmin.

UNLABELLED: We evaluated ECG-gated SPECT (g-SPECT) in the measurement of absolute left ventricular (LV) volume by comparing it with left ventriculography (LVG) and with cine-MRI. METHODS: Projection data from 31 patients were acquired with a three-headed SPECT system in 12 min using a 64 x 64 matrix with 1.5 zoom (1 pixel = 4.27 mm). The R-R interval from simultaneously acquired ECG was divided into eight frames. The end-diastolic and end-systolic volumes (EDV; ESV) and LV mass were assessed by an area-length method with manual delineation of the epi- and endocardial LV borders using midventricular vertical and horizontal long-axis images. The stroke volume, LVEF and cardiac output (CO) were generated from the EDV, ESV and heart rate during the study. The g-SPECT LV values were compared with those of LVG (25 patients) and cine-MRI (18 patients). RESULTS: The g-SPECT values correlated well with those from LVG (r = 0.83 to 0.92; p < 0.001) and cine-MRI (r = 0.76 to 0.99; p < 0.001). The g-SPECT technique provides an assessment of LV volumes (EDV, ESV, stroke volume, LVEF, CO, LV mass). CONCLUSION: Despite potential problems that may cause inaccuracy and require improvements such as an accurate and reproducible automatic edge detection algorithm, g-SPECT has clinical utility in assessing global LV volumes and function.

Location of the site of bacterial bile-salt deconjugation by combining abdominal scintigraphy with expired C-14.

A combined 14CO2 bile-salt breath and scintigraphic test has proved useful in determining the site of bile-salt deconjugation by bacteria. Data suggest that the procedure can be shortened to less than 8 hr with Tc-99m sulfur colloid abdominal scintigrams added to locate the labeled meal. Moreover the cumulative 14CO2 excretion, which is an indes of the rate of bile-salt deconjugation, gives clearer separation than peak specific activity between normals and either high or low deviations from normal, The test should be helpful in a number of difficult diagnostic problems involving chronic diarrhea, and offers as well both as well both a guide to appropriate therapy and a monitor for relapse in enfected blind-loop syndromes,

Comprehensive evaluation of renal function in the transplanted kidney.

By means of a comprehensive renal function test based on the analysis of orthoidohippurate kinetics carried out 223 times in 86 renal transplatn patients, we have been able to separate clearly five clinical entities: normally functioning transplanted kidneys, acute tubular necrosis, cell-mediated rejection, humoral (chromin) rejection, and postrenal obstruction. Accurate prediction of the fate of the rejecting kidney can be made while still subclinical as much as a week before manifestations by other techniques are evident. Data on 22 donors studied 44 times are also presented. The comprehensive test consists of measurements of effective renal plasma flow (ERPF), sequential scintigraphy, calculations of excretory index (EI) (percent dose actually found in bladder and voided urine as a fraction of the percent dose expected at a given time after injection at the patient's specific ERPF), and residual urine volume. Formulas and regression equations for the calculation of ERPF, EI, residual urine, etc., are presented.

Measurement of glomerular filtration rate: single injection plasma clearance method without urine collection.

Glomerular filtration rate (GFR) can be calculated from the plasma clearance of any of several radiopharmaceuticals that are excreted by glomerular filtration. Simplified methods have been proposed that require only one or two plasma samples in lieu of a more complete clearance curve. We examined the error introduced by this simplification. Forty patients were studied using a dual-isotope technique employing [99mTc]DTPA and [169Yb]DTPA, obtaining eight plasma samples for each clearance curve at intervals from 10 to 240 min after injection. Data were fit to several empirical or semiempirical formulae and also to a two-compartment computer model that permitted GFR estimation from only one or two data points. The computer model gave good fit, but so did several simpler methods. The error that results from replacing the complete clearance curve by a single 3-hr sample was about 8 ml/min (residual s.d.). By using two samples (at 1 and 3 hr), the error could be reduced to 4 ml/min. Recommended one- and two-sample methods are presented.

Quality control of Tc-99m DTPA for measurement of glomerular filtration: concise communication.

When technetium-99m DTPA is used to measure glomerular filtration rate (GFR), the accuracy depends on the supplier of the radiopharmaceutical. The error in GFR is due to protein binding, as we have shown by direct measurement. In 19 patients, GFR measured with Tc-DTPA and corrected for protein binding agreed with that measured simultaneously using Yb-169 DTPA (correlation coefficient 0.991). Without correction, Tc-DTPA gave falsely low values in patients having good renal function, in whom unbound activity cleared rapidly while bound activity remained in the circulation. When Tc-DTPA is used to measure GFR, the in vivo protein binding should be measured and used to correct the data.

Determination of organ volume by single-photon emission tomography.

A method for estimation of organ volume is proposed, based on analysis of individual slices obtained from SPET images. In a phantom simulating clinical circumstances, the data show that the level a threshold at 46% of the maximum activity predicts most closely the true volume over a wide range above one liter. The level at 45% predicted better volumes of less than one liter. For phantoms of 839 ml or less, the error was 6.3 ml (one standard error of estimation). This level seems to be independent of the plane or position of the phantom and also independent of the amount of scattering material around it. Nonradioactive voids ("holes") within a phantom may be included or excluded at will when their edges are not tangent to the edge of the phantom. In such cases, their edges are not distinguishable from the edge of the phantom and their volumes are excluded. Knowledge of organ volumes has both diagnostic and therapeutic importance and could lead to a more precisely quantitated total of the radioactivity contained in an organ or space.

Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA.

Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

Results of radionuclide assessment of cardiac function following transplantation of the heart.

Radionuclide assessment of ejection fraction was determined early and late postoperatively following cardiac transplantation in 16 patients. In 11 patients, ejection fraction was determined within 48 hours of an endocardial biopsy. There was no relationship between the severity of histologically evident rejection and the ejection fraction (Pearson correlation coefficient [r] = -0.11; p = 0.47). In 2 patients, severe graft fibrosis developed with consequent diminution in ejection fraction. There was no relationship between severity and duration of rejection or the amount of immunosuppression required to treat acute rejection and the development of graft fibrosis. The mean resting ejection fraction in 7 patients in follow-up ranging from 6 to 21 months after transplantation was 0.59 +/- 0.06 (standard deviation), and the mean exercise ejection fraction in 6 of these patients was 0.72 +/- 0.08. Radionuclide-determined ejection fraction is not predictive of rejection early after operation. During short-term late follow-up, systolic left ventricular function at rest and exercise has been retained at normal levels.

A comparison of the renal effects (ERPF, GFR, and FF) of FK 506 and cyclosporine in patients with liver transplantation.

1. The mean "cost" in milliliters per minute of ESLD alone, prior to transplantation, was 35% + 23% (1 SD). In GFR it was 15%. 2. The additional burden of CyA + OLT increases the loss in ERPF an additional 18%; in GFR, it increases loss another 10%. Thus, the total loss in CyA-treated patients was 53% and 25%, respectively. 3. The decrease imposed by FK 506 + OLT on ERPF was only 7%, with no decrease in GFR. 4. Therefore, from the renal point of view, FK 506 would appear to be the superior drug. 5. The large error around mean values underlines the desirability of performing these tests on the individual patient rather than on information from groups, since many values fall near the threshold of the azotemic range (ERPF approximately 175 mL/min). 6. As renal mass was compromised, ie, fall in the ERPF, the GFR increased relatively, ie, the renal filtering membrane became more permeable and the FFs gradually increased. 7. The loss of renal function was significantly less in OLT patients on FK 506 than CyA. However, the greatest loss in expected renal function was due to the basic ESLD itself.

Distinguishing avascular necrosis from segmental impaction of the femoral head following an acetabular fracture: preliminary report.

To distinguish segmental impaction from avascular necrosis of the femoral head, 26 consecutive patients who sustained an acute displaced acetabular fracture were assessed preoperatively with routine radiographs, computed tomography, and radionuclide imaging using pinhole collimation and single photon emission computed tomography (SPECT). The diagnostic criterion for avascular necrosis was a photopenic defect of the femoral head, whereas, the criterion for segmental impaction was an area of impaction of at least 1 cm2 noted at the time of surgery. Of this series, 3 incurred a segmental impaction while 1 showed evidence consistent with avascular necrosis on SPECT imaging. None of the patients possessed diagnostic features of both complications. The distinction between these two complications of an acetabular fracture should contribute to the application of appropriate surgical techniques to correct segmental impaction and avascular necrosis.

Technetium-99m MDP scintigraphy of rhabdomyolysis induced by exertional heat stroke: a case report.

A case of rhabdomyolysis induced by exertional heat stroke in a police officer recruit is reported. Technetium-99m methylene diphosphonate scintigraphy demonstrated marked uptake of the injured skeletal muscle. This bone-scanning agent provided an excellent means of localizing and evaluating the muscle injury of rhabdomyolysis. Nuclear medicine physicians should be aware of the special conditions and causes in which bone scan may demonstrate striking findings.

Phantom kidney: a CT correlation.

The phantom kidney is a "kidney-like" apparition which may be seen in dynamic renal scintigraphy typically in post-nephrectomy patients or in patients with unilateral renal agenesis. We report a case of a phantom kidney demonstrated in the angiographic phase of renal scintigraphy with 99mTc-dimercaptosuccinic acid (99mTc-DMSA) in a patient who was nephrectomized 14 years previously. After comparison with the CT images, we conclude that our patient's finding was caused by an increased mesenteric vascularity, possibly postprandial. Several conditions which may cause the phantom kidney effect, have been reported, but increased mesenteric vascularity seems to be the most common cause.

The use of quantitative scintigraphy in the measurement of portal-systemic shunting in rats.

Portal-systemic shunting was studied in 54 portal hypertensive rats both in vivo and in vitro using radioactive microspheres. The animals underwent partial portal vein ligation around needles of varying diameter to produce a wide range of shunting. Two to four weeks later, quantitative lung-liver scintigraphic and whole body images were obtained in vivo following ileocolic vein injection with 99mTc-MAA. After sacrifice, the lung and liver activities were determined by the gamma camera, a dose calibrator, and a well counter. Portal-systemic shunting ranged from 0.1-97.6%. When shunting was compared in vivo and in vitro, an excellent correlation was found (r = 0.99, p < 0.001). A subgroup of 24 animals had consecutive injections of 99mTc-MAA and 51Cr-labeled 15 microns microspheres, which, although different in size, yielded similar results (r = 0.89, p < 0.001). We conclude that in small laboratory animals a wide range of shunting can be measured accurately in vivo by quantitative scintigraphy.

ECG-gated thallium-201 myocardial SPECT in patients with old myocardial infarction compared with ECG-gated blood pool SPECT.

We evaluated one of the merits of ECG-gated thallium-201 single photon emission computed tomography (g-T1 SPECT), i.e., the ability to appreciate left ventricular (LV) wall motion. LV wall motion assessed by g-T1 SPECT and by ECG-gated Blood Pool SPECT (g-BP SPECT) was classified into three grades and compared segment by segment. T1-201 uptake by g-T1 SPECT was also classified into three grades and compared with those of wall motion in g-BP SPECT. Fifty patients with prior myocardial infarction were injected intravenously at rest with 111 to 185 M Bq (3 to 5 mCi) of Tl-201. The left ventricular regions were divided into anterior, septal, inferior and lateral segments (50 patients X 4 segments = 200 segments in total). The grades of wall motion and Tl-201 uptake detected by g-Tl SPECT correlated well with those of wall motion in g-BP SPECT (94.5% and 85%, respectively). With g-Tl SPECT it was possible to evaluate left ventricular wall motion, providing clear perfusion images.