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Purpose: Diagnosing brain death is important in managing the comatose patient for whom the continuation of life support is being questioned and when organ harvesting is being considered. The virtual immediate localization of Tc-99m HMPAO to cerebral and cerebellar tissue provides an index of blood perfusion, and its absence denotes brain death. Other methods for assessing brain death include cerebral angiography, MRI, CT imaging after inhalation of stable xenon, electroencephalography, and clinical examination. The contrast material used for angiography may damage harvested organs, and the other studies have significant errors. MRI, CT imaging, and angiography are unsuitable for bedside use., Methods: Twenty-three patients, who presented with head trauma, prolonged anoxia or intrinsic brain disease (e.g., glioblastoma multiforme) and who were brain-dead by clinical examination criteria, were referred to the nuclear medicine division for verification of brain death. For adults, approximately 25 mCi Tc-99m hexamethylpropylene amineoxime (HMPAO) was administered intravenously. All patients but one were imaged using a mobile scintillation camera at the bedside., Results: We demonstrated (1) both cerebral and cerebellar perfusion, (2) neither cerebral nor cerebellar perfusion, (3) cerebral without cerebellar perfusion, and (4) cerebellar without cerebral perfusion. Patients without cerebral perfusion were diagnosed as brain-dead. The significance of a viable cerebellum in the absence of cerebral viability was not fully appreciated, although organs were harvested from such patients. We determined how well the clinical examination criteria held up in the diagnosis of brain death against the new gold standard of Tc-99m HMPAO scintigraphy: Clinical examination criteria correctly predicted brain death only 83% of the time compared with HMPAO scintigraphy., Conclusions: Brain death assessment by Tc-99m HM-PAO scintigraphy has proved to be a reliable, safe, and cost-effective bedside method and may have practical application in the assessment of brain death in potential cadaveric donors.

It has been widely accepted that the organ transplantation has become one of the choices for the therapy of end-stage diseases (kidney, heart, liver, lung, etc.). However, organ transplantation requires extremely high cost and heavy psychological burden for his/her family. Therefore, and moreover to reward the donor's good will, it must be highly successful. Nuclear medicine tests can offer reproducible functional information with and without images. Repeat tests can be performed easily. These characteristics are suitable not only for preoperative evaluation of donors and recipients but also for monitoring the transplanted organs. Therefore, nuclear medicine can potentially play an important role in organ transplantation. Competitive diagnostic modalities such as US, CT, MR are also progressing and very useful in some situation in organ transplantation. Nuclear medicine physicians and technologists should be aware of the merits and the role of nuclear medicine in organ transplantation and should try to prepare for good service to provide useful information. This article reviews the role of nuclear medicine in organ transplantation, demonstrating representative cases.

Purpose: The authors studied the relation between cardiac output (CO) and effective renal plasma flow (ERPF) and compared values from control patients with various cardiac problems with those in a group of study patients who had undergone heart transplantation., Methods: The experimental group was divided into three subgroups according to the interval between the time of surgery and the time of the CO-ERPF studies. Group 1 consisted of patients studied fewer than 10 days after surgery; group 2 consisted of patients studied 10 to 20 days after operation; and group 3 consisted of patients studied more than 20 days after operation. Effective renal plasma flow was determined by the single-injection, single plasma sample method, where 50 microCi I-131 orthoiodohippurate was injected intravenously in a single dose and plasma concentrations of radioactivity were determined. The quotient of injected dose radioactivity divided by plasma radioactivity is highly predictive of global ERPF. Cardiac output was measured by thermodilution., Results: In the control group, a positive linear correlation was found between CO and ERPF; however, the CO:ERPF ratio was elevated, and after heart transplantation, a lag time was observed for as long as 3 weeks in some patients before CO:ERPF ratios returned to control group levels. The regression equation and standard error for the control group was CO = 1.85 + 0.0065 ERPF (+/-0.62) l/min versus 1.433 + 0.0068 ERPF (+/-0.64) l/min for group 3. The correlation coefficients comparing CO with ERPF were r = 0.88, 0.23, 0.51, and 0.85, for the control group and groups 1, 2, and 3, respectively., Conclusion: A localized release of catecholamines from the adrenal gland is proposed to cause ERPF damping after abrupt increases in CO.

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.

Gallium-67 is routinely used for follow-up of patients with malignant melanoma. However, its nonspecificity for melanoma and its high rate of false-positive results have always been a matter of concern. The authors describe a patient who encountered serious problems with the use of gallium. Because gallium is taken up well by the liver and by melanoma, results of gallium scintigraphy of the liver may appear normal even if there is metastatic disease. In this patient, results of gallium scintigraphy of the liver were negative for metastasis but revealed extrahepatic foci detected by the monoclonal antibody. Computed tomography showed areas of attenuation, revealing only a few intrahepatic tumors and no extrahepatic disease. Tc-99m SC revealed intrahepatic metastases, but no extra-hepatic metastases were seen. A monoclonal antibody (ZME-018) scintigram did reveal hepatic metastases along with probable small, extrahepatic, metastatic foci. Overall hepatic uptake of the monoclonal antibody was relatively low. An image subtraction algorithm was devised whereby the sulfur colloid image was subtracted from the gallium scintigram. The resultant image revealed both the intrahepatic and extrahepatic metastases seen on the ZME-018 images. It is likely that in the past many hepatic metastases have been missed because Tc-99m SC images have not been routinely used as part of melanoma management protocols. The uptake of the ZME-018 by the tumor was significantly higher than that of the normal liver, suggesting that ZME-018 labeled with the appropriate emitter may be an effective specific therapeutic tool in selected patients.

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.

We previously reported that brain single-photon emission tomography (SPET) images could be improved by using an attenuation coefficient map constructed with transmission data and the iterative expectation maximization (EM) algorithm. However, the conventional EM algorithm (CEM) typically requires 30-80 iterations to provide acceptable results, limiting its clinical applicability. Several methods have been proposed to accelerate the EM algorithm. The purpose of this study was to search for a practical method for accelerating the EM algorithm. The methods investigated here include the accelerated EM algorithm (ACEM) using additive correction, ACEM using multiplicative correction, and Tanaka's filtered iterative reconstruction method (FIR). These methods were assessed by simulated SPET studies of a phantom incorporating nonuniform attenuation and by reference to clinical brain SPET data. In the simulation studies, the above methods were evaluated by using three parameters (root mean square error, log likelihood value, and contrast recovery coefficient); the results showed that FIR had an advantage over other methods in terms of all parameters. The results obtained using the clinical data demonstrated that FIR could reconstruct acceptable images in only five iterations. These results show that FIR offers significant advantages over CEM or other ACEMs, indicating that FIR can make the EM algorithm practical for clinical use in SPET.

The increased incidence of infection in cirrhotics may in part be attributable to dysfunction of the reticuloendothelial system (RES) in removing pathogens from the circulation. The portosystemic shunting (PSS) that results from portal hypertension in cirrhotics may compromise RES function by allowing enteric pathogens to be shunted away from the Kupffer cells. A well-characterized model of portal hypertension induced by partial portal vein ligation (PVL), in which there is no hepatic parenchymal cell damage, was used. Kupffer cell function is unaltered and the effect of PSS alone on overall RES function can be evaluated. In addition to the usual immunologically inert [99mTc]sulfur colloid, an actual pathogen was also evaluated. PVL and sham-ligated rats were given either [99mTc]sulfur colloid or E. coli via the ileocolic vein. The right femurs, lungs, livers and spleens of the animals receiving 99mTc were excised and the radioactivity counted. The lungs, livers, and spleens of the animals receiving E. coli were liquefied and the bacteria were quantified. For both groups the ratios of 99mTc or E. coli in the lung, spleen, and femur to liver were calculated. PVL rats had significantly more 99mTc in the lung, spleen, and femur than the sham rats. There were also significantly more E. coli in the lungs for PVL rats but no significant difference in the spleen counts. These results imply that even in the absence of Kupffer cell dysfunction, PSS alters reticuloendothelial system function by causing a greater distribution of pathogens to the periphery. This altered distribution may contribute to an increased susceptibility to infection in cirrhotics.

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.

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.

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.

Fifty-five hepatobiliary scintigraphic studies using 99mTc-Mebrofenin were performed in 52 orthotopic liver transplant patients to evaluate suspected biliary complications, namely biliary extravasation and extrahepatic obstruction. Final diagnosis was made by analysis of the clinical course and other procedures. Three out of three studies of biliary leak and four out of five studies of biliary obstruction were detected. There were no false positives in either complication. The sensitivity, specificity and accuracy were 100, 100, 100% for ectravasation and 80, 100, 98% for obstruction, respectively. Hepatobiliary scintigraphy appears to be an accurate means of detecting biliary leak and obstruction associated with the transplanted liver.

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.

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.

In rats with partial portal vein ligation, 95 +/- 0.9% of the splenic blood flow is shunted from the portal to the systemic circulation when an intrasplenic injection of microspheres is used to determine the degree of shunting. Despite this magnitude of portal-systemic shunting, several biochemical and endocrine consequences of portal-systemic shunting occur at levels below what is expected for the degree of shunting found. In an effort to resolve these discordant findings, shunting from both the splenic and the mesenteric bed was studied in anesthetized portal hypertensive rats with various degrees and/or duration of portal vein stenosis. The shunting from the mesenteric bed averaged 66.7 +/- 29.9% (range 5.1-99.1%) and was influenced both by the degree and duration of portal vein stenosis. In contrast, shunting from the splenic bed averaged 97.3 +/- 4.0% (range 79-99.9%) and demonstrated no variation between groups determined by the degree of portal vein stenosis. The shunting from the splenic bed was consistently greater than that found from the mesenteric bed. Mesenteric but not splenic shunting correlated with serum bile acid levels. Mesenteric shunting was related inversely to the weight-adjusted liver mass and to serum testosterone levels. Based upon these data obtained in portal hypertensive rats, it is concluded that splenic injections of microspheres overestimate portal-systemic shunting. In contrast, mesenteric injections of microspheres yield values for shunting that correlate well with independently determined biochemical and endocrine consequences of shunting. These observations support the validity of the mesenteric shunting measurements obtained.

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.

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.

A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

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.

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.

Estimation of effective renal plasma flow (ERPF) can be made easily, inexpensively, and accurately by means of a single plasma concentration determination, sampled 44 min after injection of 131I-orthoiodohippurate (OIH). We originally established predictive regression equations based on a series of patients with a wide variety of diseases and a few normal potential kidney donors. The equation best fitting that data was parabolic in form and assumed a negative slope when high ERPF rates were encountered. This problem has been corrected by deriving new equations (parabolic and exponential) based on an expanded series which includes a large number of subjects with high ERPF. Errors of estimation are lower than those of the more classic para-aminohippuric acid (PAH) clearances and well within the exigencies of clinical practice.

This report deals with the diagnosis of perforation of the common bile duct into the lesser sac by HIDA cholescintigraphy. The first hour images after injection were suggestive of biliary obstruction. Subsequent images demonstrated unusual accumulations of the activity into the lesser sac and retroperitoneal potential spaces. Careful correlation between scintigraphic and surgical findings were undertaken. The case is reported to demonstrate the scintigraphic findings in choledochal perforation and to stress the importance of carrying out late images when the initial ones are abnormal.

In the management of patients with congestive heart failure (CHF), it is often desirable to have precise knowledge of overall renal function, including the effective renal plasma flow (ERPF). It has long been recognized that ERPF is diminished in CHF. Since glomerular filtration rate is often decreased to a much lesser extent, other noninvasive procedures such as the measurement of creatinine clearances may not be entirely suitable. ERPF determination by the single plasma sampling (SPS) method affords a rapid, simple, noninvasive, and economical technique that is quite accurate and reproducible. A SPS method has been well-tested in patients following renal transplantation plus a wide variety of nephrological disorders. We have been concerned whether the SPS method would be valid in volume expanded patients. In 28 determinations of ERPF in patients with CHF, and in five patients who did not have CHF, we have found the SPS estimation of ERPF to yield results that are not clinically significantly different from those obtained by the detailed compartmental analysis method. The volumes of 131I-orthoiodohippurate (OIH) distribution were found to be somewhat higher in CHF than in controls, but fractional rate constants were proportionately lower so that intercompartmental flow rates and OIH concentrations were not different from controls. Therefore, the SPS estimation of ERPF is valid in patients with CHF and may be useful in monitoring the renal effects of various hemodynamic and pharmacological interventions.