Tc-99m hexamethylpropylene amine oxime scintigraphy in the diagnosis of brain death and its implications for the harvesting of organs used for transplantation.

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.

[Role of nuclear medicine in organ transplantation].

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.

I-131 orthoiodohippurate assessment of renal function after heart transplantation.

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.

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.

In-111 monoclonal antibody versus Ga-67 citrate and Tc-99m SC subtraction in a patient with malignant melanoma.

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.

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.

An evaluation of the accelerated expectation maximization algorithms for single-photon emission tomography image reconstruction.

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.

Effect of isolated portal hypertension on Kupffer cell function.

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.

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.

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.

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.

Detection of complications after liver transplantation by technetium-99m mebrofenin hepatobiliary scintigraphy.

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.

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.

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.

Evaluation of portal-systemic shunting in rats from mesenteric and splenic beds.

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.

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.