Myocardial uptake and clearance of thallium-201 in normal subjects: comparison of dipyridamole-induced hyperemia with exercise stress.

Thallium-201 uptake and clearance after dipyridamole infusion may differ from that after exercise stress because the hemodynamic effects of these two interventions are different. In this study of normal volunteers, thallium kinetics after dipyridamole (n = 13) were determined from three serial image sets (early, intermediate and delayed) and from serial blood samples and compared with thallium kinetics after exercise (n = 15). Absolute myocardial thallium uptake was greater after dipyridamole compared with exercise (p less than 0.0001), although the relative myocardial distribution was similar. The myocardial clearance (%/h) of thallium was slower after dipyridamole than it was after exercise. Comparing dipyridamole and exercise, the differences in clearance were large from the early to the intermediate image (anterior, -11 +/- 17 versus 24 +/- 5, p = 0.0005; 50 degrees left anterior oblique, -7 +/- 11 versus 15 +/- 8, p = 0.004; 70 degrees left anterior oblique, 3 +/- 9 versus 21 +/- 6, p = 0.001). In contrast, the differences in clearance were small from the intermediate to the delayed image (anterior, 15 +/- 4 versus 20 +/- 2, p = 0.025; 50 degrees left anterior oblique, 15 +/- 4 versus 19 +/- 3, p = 0.13; 70 degrees left anterior oblique, 15 +/- 3 versus 18 +/- 2, p = 0.047). Thallium uptake and clearance in the liver, splanchnic region and spleen were greater after dipyridamole (p less than 0.001). Blood thallium levels were greater after dipyridamole (p less than 0.05) and cleared more slowly (p = 0.07). Thus, myocardial thallium-201 uptake and clearance after dipyridamole infusion differ from thallium kinetics after exercise. This difference is, in part, related to associated differences in extracardiac and blood kinetics. Diagnostic criteria for the detection of abnormal thallium-201 clearance must be specific for the type of intervention.

Blood flow of human soft tissue sarcomas measured by thallium-201 scanning: prediction of tumor response to radiation.

Thallium-201 chloride (201T1) has been used to determine regional perfusion in the myocardium and in tumors. This study was done to determine the potential prognostic importance of lesion tracer uptake to regression, local control, and rate of distant metastasis in 14 patients with neoplasms of soft tissue. Most patients had planned resections following preoperative radiation therapy. Minimum follow-up was 4 years. The ratio of nuclide uptake in the tumor to surrounding normal tissue was used as an estimate of relative blood flow. Tumors with acute volume responses (greater than or equal to 50% at the completion of X irradiation) had lower 201T1 uptake indicating lower relative blood flow than tumors that failed to have a volume reduction [1.63 +/- 0.30 (n = 9) vs 3.49 +/- 0.41 (n = 5) 201T1]. All patients had local tumor control. Patients with high uptake tumors tended to develop metastases at a higher frequency, although this was not statistically significant (p = 0.10). We conclude that 201T1 scans are a safe, non-invasive method of estimating tumor perfusion which can be useful to predict acute response to radiation, and may help to identify patients who will ultimately develop distant metastases.

Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase.

OBJECTIVES: Reversal of the hematologic and visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated. METHODS: To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months. RESULTS: The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients. CONCLUSIONS: Prolonged treatment over 3 1/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked improvement occurs in marrow composition and bone mass in both children and adults.

Accumulation of 99mTc-diphosphonate in four patients with hepatic neoplasm: case reports.

The accumulation of bone-seeking radiopharmaceuticals in extraosseous lesions has been reported in patients with myocardial infarctions, cerebral infarctions, and some soft-tissue tumors. While the precise mechanisms involved remain uncertain, the spectrum of abnormalities exhibiting such accumulation increases. In our laboratory, 99mTc-diphosphonate concentrated in four hepatic tumors (one cholangiocarcinoma and three metastases from colon carcinoma). This property of phosphate-related radiopharmaceuticals has not been reported previously. Awareness of the possibility of focal diphosphonate accumulation in the liver should help avoid confusion with right lower rib-cage metastasis or pleural effusion.

Quality of bone scans compared with time between dose and scan.

The usual time interval between the administration of technetium-labeled bone-seeking radiopharmaceuticals and imaging varies among nuclear-medical departments. Pharmacokinetic data indicate that the interval could be as short as 2 hr. We have studied overall quality of bone detail in 280 bone scans performed at intervals varying from 2 to 5 hr following injection of technetium-99m diphosphonate. No significant qualitative difference was found between the studies performed at 2 hr and those done at later intervals.

A modified method for the in vivo labeling of red blood cells with Tc-99m: concise communication.

The rate of incorporation of Tc-99m into red blood cells pretinned in vivo was measured by collecting blood samples in stannous DTPA solution, which served as a competing ligand for Tc-99m. This collection technique permitted a measurement of high-affinity red-cell labeling efficiency at the instant of sampling. At 0.5 min after injection only 62% of technetium is tightly bound to the red cell; this rises to 94.5% at 10 min. Based on the graded labeling of the red cells, the in vivo labeling procedure was modified by isolating pertechnetate and red blood cells tinned in vivo in a syringe during the first 10 min of labeling. The pertechnetate is thus prevented from distributing to extravascular compartments, and 90% of the injected Tc-99m is firmly bound to red blood cells at the time of injection. In a series of 23 patients, seven were tested with the in vivo method and seven with the modified in vivo method, and nine patients were tested with each method on separate occasions. A decrease in gastric activity and improved image quality were found with the modified method compared with the standard method of in vivo red-cell labeling.

Characterization of the reinjection thallium image.

The 201TI image after reinjection was characterized by analysis of stress and reinjection data acquired in 204 consecutive patients undergoing planar 201TI cardiac stress tests. In an additional 63 patients, redistribution data were also acquired to determine the effect of washout on the final reinjection image. Maximum count densities for the myocardium, lung and liver were measured, and the ratios between the stress and redistribution and the stress and reinjection sets of data were calculated. In patients with < 5% probability of coronary artery disease (CAD) ("normal" group), the reinjection image was typified by less myocardial activity (initial/reinjection = 1.22), slightly less lung activity (initial/reinjection = 1.05) and greater hepatic activity compared to the initial postexercise image. In male patients with > 5% probability of CAD, peak myocardial activity after reinjection was affected by the following variables: the interval between stress and reinjection, the amount of the initial dose and the 201TI scan results (normal 201TI study: initial/reinjection = 1.16; abnormal = 1.06; p < 0.009). Myocardial activity after reinjection was linearly related to myocardial activity after redistribution (r = 0.82). There was no significant influence by those variables in the 76 women who were studied. In conclusion, myocardial 201TI was decreased after reinjection in normal patients. The results indicate that there is an increased likelihood of underlying CAD in male patients undergoing exercise stress tests when 201TI myocardial activity on reinjection is greater than on the initial image.

Redistribution of visceral blood volume in upright exercise in healthy volunteers.

Exercise induced changes in the blood volume of visceral organs (cardiopulmonary and liver, spleen, and kidneys) were determined by scintillation camera imaging of the distribution of technetium-99m-labeled red blood cells in the thorax and abdomen of ten healthy adult volunteers. Graded upright bicycle exercise was performed to the point of exhaustion with the volunteer positioned with his/her back to the scintillation camera and data recording was synchronized to the pedal cycle to minimize patient motion artifacts within the data. The first image from each level of exercise was analyzed by placing regions of interest over the spleen, liver, kidneys, and right lung. The counts in each organ were expressed as a percent of activity at zero workload. Analysis of data using Hotelling's t-squared analysis to see if overall differences existed between the last four measurements (up to the time of exhaustion) regarding percent change from baseline for spleen, kidney, liver, and right lung were made. The splanchnic bed had a significant decrease in blood volume. The spleen decreased 39%, while the liver decreased 14%. For the kidney and liver, no significant differences were achieved (p greater than 0.24, p less than 0.15, respectively). The lung increased its blood volume to 128% of control, significant with p less than 0.02. This data demonstrates that in healthy volunteers there is normal redistribution of blood volume during maximal exercise with a significant reduction in blood volume of the spleen as well as a significant rise in blood volume within the lungs.

Technetium-99m-human serum albumin: evaluation of a commercially produced kit.

Results are reported on the use of a commercial kit for the labeling of human serum albumin with 99mTc. One-hour blood levels obtained in 20 subjects undergoing gated cardiac imaging were found to be 46.0 +/- 10.5% (s.d.) of the administered dose. The highest labeling efficiencies (94.2 +/- 9.3%) were obtained when human serum albumin 25% (salt-poor) was used. Satisfactory nuclear cardiac ventriculographic images were obtained in patients receiving the radiopharmaceutical when the labeling efficiency was at least 85%. Occasional batches were milky in appearance, contained black particulate matter, were acidic, or contained a high percentage of unbound 99mTc activity. Although this kit makes 99mTc-human serum albumin accessible to most nuclear medicine facilities for general clinical use, an active quality control program is required prior to use in patients.

Early diagnosis of disc-space infection using Gallium-67.

A 4-year-old boy had had progressive central lumbar pain and hamstring spasm. He had a normal lumbar-spine x-ray except for minimal L-5, S1 spondylolysis, but gave an abnormal gallium-67 scan in the region of the low lumbar spine. Eight weeks following intensive antibiotic therapy, confirmation of the diagnosis of disc-space infection was established by roentgenographic studies that demonstrated narrowing of the L 4-5 intervertebral disc space. A technetium-99m diphosphonate bone scan, performed concurrently with the gallium-67 study, was normal.

Evaluation of gastrointestinal bleeding by red blood cells labeled in vivo with technetium-99m.

To determine the effectiveness of abdominal imaging with RBCs labeled in vivo with Tc-99m, for the detection of gastrointestinal (GI) bleeding, 28 control subjects and ten patients with suspected bleeding underwent scintigraphy at 0-24 hr after tracer injection. Colonic activity was noted in one of the controls within 3 hr of injection, and in five of ten controls at 24 hr, all of whom had initial gastric activity. Of the ten patients with suspected GI bleeding, eight had documented active bleeding; seven of these had positive scintigrams. Nasogastric (NG) suction markedly decreased the presence of initial gastric activity in the patients with active bleeding. With this blood-pool radiopharmaceutical, frequent imaging of the abdomen over 24 hr can be done to test active bleeding. Continuous NG suction is recommended to reduce accumulation of gastric activity. These results suggest that red blood cells labeled in vivo with Tc-99m provide a sensitive method of detecting active GI bleeding.

Improved brain scan specificity utilizing 99mTc-pertechnetate and 99mTc(Sn)-diphosphonate.

Each of 36 patients was studied with two separate brain scans performed sequentially after the injection of 20 mCi of 99mTc-pertechnetate or 20 mCi of 99mTc(Sn)-diphosphonate. The resulting scans were qualitatively compared, and lesion-to-nonlesion ratios of activity determined. Diagnoses were established by clinical criteria and were supported in the majority of cases by computerized axial tomography or roentgen angiography or both. Histologic confirmation was available in five cases of tumor and in the single cases of subdural hematoma and cerebral abscess. Of 22 cerebral infarctions, 15 were better demonstrated with 99mTc-(Sn)-diphosphonate than with 99mTc-pertechnetate. Of the seven remaining cases, three were visualized equally well with each agent, and three were better demonstrated with 99mTc-pertechnetate. One was not seen with either agent. Of the 12 tumors, 11 were visualized better with 99mTc-pertechnetate than with 99mTc-(Sn)-diphosphonate while in one case the lesion was seen equally as well with both agents. In no case was a lesion definitely seen with one radiopharmaceutical and not with the other. These results indicate that this dual method is helpful in differentiating gliomas and metastases from cerebral infarctions.

Prognosis in Stage 1 malignant melanoma: seven-year follow-up study of splenic radiocolloid uptake as predictor of death.

In an earlier study we found that patients with clinical Stage 1 and 2 cutaneous malignant melanoma and increased splenic radiocolloid uptake had more frequent recurrence at 24 mo, compared with melanoma patients having normal liver-spleen scintigrams. This report, an 80-mo follow-up study, gives further information on 119 clinical Stage 1 patients. Fifteen of 35 patients with increased splenic uptake (42.9%) died from melanoma as opposed to only 16 of 84 (19.1%) with normal liver-spleen images (p less than 0.01). Multivariate analysis showed that augmented splenic uptake of technetium-99m sulfur colloid is a marker for adverse prognosis in patients with malignant melanoma but does not appear to be an independent variable in predicting death. In clinical Stage 1 patients, increased splenic uptake correlated significantly with pathologic stage (positive elective node biopsy) as well as thickness and mitotic rate in patients with thicker lesions. It may be that patients with thicker, pathologically aggressive tumors have an increased splenic blood flow and/or enhanced immune and reticuloendothelial response (as manifested by abnormal liver-spleen scintigram). If so, the enhanced immune response does not appear to contribute to overall survival.

Diffusing capacity is not measurably affected by routine lung perfusion scanning.

Lung scanning with radiolabeled macroaggregated albumin (MAA) has caused cardiovascular collapse and death in patients with extensive pulmonary vascular disease. These adverse reactions have been suggested to be secondary to MAA embolic occlusion of a significant portion of the remaining pulmonary circulation. The single breath diffusing capacity for carbon monoxide (SBDLCO) is heavily dependent on the status of the pulmonary microcirculation and is reduced in clinical pulmonary embolism. The effect of MAA particles on the lung microcirculation was measured by SBDLCO in 11 patients undergoing clinically indicated lung perfusion scanning. SBDLCO was measured before and immediately after injection of 256,000 to 448,000 20-40 micron particles of [99mTc]MAA. Mean SBDLCO prior to injection was 18.9 +/- 1.7 (s.e.m.) and immediately after injection was unchanged at 19.0 +/- 1.6 ml/min/mmHg. The lowest pre-injection SBDLCO values were 11.5 and 6.2 ml/min/mmHg (54% and 28% of predicted, respectively); in neither of these patients was there a detectable change in SBDLCO measured after injection of MAA. Thus occlusion of as many as 448,000 20-40 micron pulmonary vessels by MAA is without detectable impact on the transfer of carbon monoxide even in patients with sufficient pulmonary disease to lower the SBDLCO to 28% of predicted.

Ventilation-perfusion scintigraphy in the PIOPED study. Part I. Data collection and tabulation.

The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study of more than 700 patients is the largest existing study of the accuracy of lung scintigraphy in the diagnosis of acute pulmonary embolism. Perfusion scans were obtained in all patients and ventilation scans in almost all, using standardized techniques. Chest radiographs were obtained in all patients within 12 hr of the lung scan. Most patients underwent pulmonary arteriography. The images were interpreted according to a set of interpretive criteria which remained constant throughout the trial. A standardized, detailed description of each image set was derived by consensus of teams of two readers blinded to clinical and arteriographic findings. This communication reports the methods used to describe and categorize the ventilation-perfusion scintigrams obtained in patients who were enrolled in the PIOPED study. Scintigraphic technique is reviewed briefly, probability assessment is described and the scan description is reviewed in detail. The form used to describe the findings on ventilation-perfusion scans is reproduced. Use of this standardized description permits retrospective evaluation of the PIOPED interpretive criteria. In addition, it represents a rigorous approach to scan analysis which could facilitate application of formal interpretive schemes and enhance the reproducibility of lung scan interpretations in the clinical setting.

Ventilation-perfusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations.

This article presents an evaluation of the criteria used for categorical interpretation of the ventilation-perfusion (V/Q) scans performed in the PIOPED study. In addition, the correlation of percent probability estimates with the actual frequency of pulmonary embolism (PE) is presented. Cases which met the PIOPED criteria for various diagnostic categories were selected by computerized search of the detailed scan descriptions that had been done as part of the study. The process by which the scans were described was detailed in Part I of this report. Most of the criteria appropriately categorized V/Q scans which satisfied them. However, we recommend that three criteria should be reconsidered: 1. A single moderate perfusion defect is appropriately categorized as intermediate, rather than as low probability. 2. Extensive matched V/Q abnormalities are appropriate for low probability, provided that the chest radiograph is clear. On the other hand, single-matched defects may be better categorized as intermediate probability. Although due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. 3. Two segmental mismatches may not be the optimum threshold for high probability, and in some cases should be considered for intermediate probability. However, due to the small number of cases with this finding, no definite, statistically founded recommendation can be made. We suggest that the revised criteria resulting from these adjustments should now be used for the interpretation of V/Q scans.

The significance of augmented radiocolloid uptake by the spleen in patients with malignant melanoma.

Increase in splenic uptake of Tc-99m sulfur colloid was noted in 47 of 147 (32%) patients with cutaneous malignant melanoma early in the coure of disease. Patients with disseminated disease and/or clinical or laboratory evidence of hapatic dysfunction were excluded from study. Recurrence rate of 2 yr was higher for those patients with splenic scans demonstrating augmented uptake compared with patients having normal scans, 36% against 16% (p less than 0.02). These differences resulted from a much more favorable prognosis in women with normal scans contrasted with women with increased uptake, 6% against 26% (p less than 0.05). Women with increased splenic uptake, and all men regardless of scan status, seemed to have a higher rate of recurrence than women with normal spleen scans. Scan status may be an adjunctive prognostic marker in women.

Noninvasive estimation of pulmonary arterial pressure by analysis of pulmonary blood-flow distribution.

To determine whether a correlation exists between pulmonary arterial (PA) pressure (Pa) and the distribution of pulmonary blood flow, this distribution was measured in four upright dogs in the control state and during intravenous infusions of epinephrine or prostaglandin F2 alpha. During suspension of respiration, 15 mCi of Xe-133 were injected intravenously, and perfusion and equilibration lung images were recorded with a scintillation camera. The procedure was performed several times on each dog, with and without pharmacological elevation of PA pressure by 5 to 50 cm H2O. For each scintigram, the relative blood flow per unit ventilated lung volume (F) was plotted against centimeters above the hilum (h). Pulmonary arterial pressure was derived from each curve, assuming the relation F = B(Pa - hD)2, where B = constant and D = specific gravity of blood. Calculated PA pressure correlated strongly (r = 0.83) with measured PA pressure, suggesting a possible means of noninvasive estimation of PA pressure.

Initial assessment of a simple functional image of ventilation.

Several methods for quantitatively measuring regional ventilation using an inert gas such as Xe133 have been described. One such method provides a functional image of washout. A particularly simple functional image may be derived from the mean transit time for clearance. Regional ventilation may thus be represented as a single image in which the spatial distribution of washout from multiple small regions of the lung is displayed. In 100 patients for whom such a functional image of ventilation was obtained, the functional image was found to be generally more useful and easier to interpret than sequential images taken during the period of washout. Distributions of half-time (t1/2) for washout and the mean transit time (t) in the same population were similar in shape, but the t distribution peaked about 15 sec later than the t1/2 distribution. The mathematical simplicity of the functional image described here should permit its implementation on virtually any nuclear medicine computer system.

Techniques for positron scintigraphy of the brain.

Positron scintigrams were obtained in normal subjects and in patients with intracranial tumors and cerebral vascular disease, using a multicrystal positron camera. The radiopharmaceuticals were 68Ga complexed with adenosine triphosphate (68Ga-ATP), 13N-ammonia (13NH3), and 15O2. Six clinical cases are described to illustrate the different cerebral distributions of intravenously administered 68Ga-ATP, 13NH3, and inhaled 15O2. The possible value of these agents in the study of cerebral metabolism and in differential diagnosis of intracranial disease is discussed.