Skeletal blood flow: implications for bone-scan interpretation.

The dispersion of the skeleton throughout the body and its complex vascular anatomy require indirect methods for the measurement of skeletal blood flow. The results of one such method, compartmental analysis of skeletal tracer kinetics, are presented. The assumptions underlying the models were tested in animals and found to be in agreement with experimental observations. Based upon the models and the experimental results, inferences concerning bone-scan interpretation can be drawn: decreased cardiac output produces low-contrast ("technically poor") scans; decreased skeletal flow produces "photon-deficient" lesions; increase of cardiac output or of generalized systemic blood flow is undetectable 1--2 hr after dose; increased local skeletal blood flow results from disturbance of the bone microvasculature and can occur from neurologic (sympatholytic) disorders or in association with focal abnormalities that also incite the formation of reactive bone (e.g., metastasis, fracture, etc.). Mathematical solutions of tracer kinetic data thus become relevant to bone-scan interpretation.

Studies of skeletal tracer kinetics. IV. Optimum time delay for Tc-99m(Sn) methylene disphosphonate bone imaging.

The kinetics of the skeletal tracer Tc-99m(Sn)methylene diphosphonate (Tc-MDP) were studied in four older patients without significant bony disease by means of compartmental analysis. Solution of the model was obtained by digital computer techniques. Tracer concentrations for "target" and "background" areas (to reflect "bone" and "soft-tissue" regions) as time functions were generated for three different imaging criteria: counting rate, a figure of merit, and contrast. The figure of merit reached a maximum early in the second hour after dose administration, but contrast was found to attain a plateau at 6 hr. Either of these criteria is in accord with recommendations in the literature for optimal imaging delay time with Tc-MDP. Bone biopsy in one patient was in good agreement with the model's prediction. Compartmental analysis provides an objective method for determining the optimal imaging delay time, depending on the criterion chosen. The method can be used for any radiopharmaceutical if the compartmental model is known and can be solved.

Studies in skeletal tracer kinetics. V: Computer-simulated Tc-99m (Sn)MDP bone-scan changes in some systemic disorders: concise communication.

Using compartmental analysis techniques, we modeled the biodistribution of Tc-99m(Sn)methylene diphosphonate in humans on a computer, and by selectively perturbing appropriate rate constants, we simulated changes in contrast between bone and soft tissue in a number of systemic disorders. The model predicts low contrast in patients with moderate to marked edema, obesity, congestive heart failure or decreased cardiac output states and high contrast with as little as 25% increase in bone avidity for the tracer. In acute renal failure without fluid-volume imbalance, image contrast should be normal. The model predicts greater contrast shortly after injection in patients with increased cardiac output, skeletal blood flow, or bone avidity; images made at these times would be indistinguishable. These simulations are in keeping with reports in the literature of bone images and bone-to-soft tissue ratios in many of these conditions, suggesting that modeling studies could play an important role image interpretation.

Bone scanning in the adductor insertion avulsion syndrome ("thigh splints").

Shin splints is a defined clinical entity resulting from extreme tension on muscles inserting on the tibia, resulting in periosteal elevation which is detectable by bone scanning. The clinical equivalent in the thigh has been described. We found scintigraphic changes in the femurs of seven short, female, basic trainees at the Fort Dix Army base, most of whom were referred for stress fractures elsewhere in the lower extremities. The scan findings were generally noted in the upper or mid femurs, always involved the anteromedial cortex, and were bilateral in five of the seven subjects. The abnormalities were linear and suggested periosteal elevation, and did not have the typical appearance of stress fracture. Since the findings correspond to the insertion of one or more adductor muscle groups, the descriptive term "adductor insertion avulsion syndrome" or "thigh splints" is proposed for this entity.

Studies of skeletal tracer kinetics: II. evaluation of a five-compartment model of [18F]fluoride kinetics in rats.

We have evaluated a five-compartment model of [18F]fluoride kinetics in rats. The initial fluoride distribution was found to be similar to that of [77Br]bromide, a known extracellular-fluid (ECF) tracer, in agreement with the hypothesis underlying the model, and the measured uptake rate in rat bones compared well with the digital computer solution. Simpler models did not give a better fit. In dead rats, fluoride movement was found within the skeleton, presumably from bone ECF to bone substance, although not as rapidly as predicted or found in the live animal. Evaluation of the rate constants permitted estimates to be made of cardiac output, skeletal blood flow, and bone ECF volume, all in accord with independent measurements. It is suggested that skeletal blood flow at rest is a constant fraction of body weight, and probably subserves a hematopoietic as well as a mineralization function.

Thallium-201 SPECT increases detectability of thyroid cancer metastases.

Thallium-201- (201Tl) chloride is known to accumulate in metastatic foci of differentiated thyroid carcinoma, but small and deep-seated lesions are generally not detectable by planar imaging. We have evaluated the use of 201Tl-chloride single-photon emission computed tomography (SPECT) in 41 post-thyroidectomy patients with differentiated thyroid carcinoma and one with medullary carcinoma; planar imaging alone was done in eight additional patients (total 50). Of 20 patients with known metastatic disease, planar 201Tl images were positive in 12 (60%) but SPECT revealed an additional 5 (25%) who had metastases (total 85%). SPECT revealed foci as small as 1.0 cm in the neck and 1.5 cm in the lungs, and was particularly useful in detection of disseminated micronodular pulmonary metastases, especially in patients whose scans were negative with diagnostic doses of 131I. Some pitfalls in interpretation of the tomographic reconstructions were found. Thallium-201 SPECT is a marked improvement over planar imaging in the detection of metastases of differentiated thyroid cancer.

Studies of skeletal tracer kinetics. I. Digital-computer solution of a five-compartment model of [18F] fluoride kinetics in humans.

We have developed a new model of short-term fluoride kinetics in humans and have solved the model on a digital computer using the SAAM-25 program. The solution accords well with available data. About 60% of intravenously administered [18F] fluoride is taken up by bone. Evaluation of the rate constants of tracer egress from blood indicates that about 17% of the cardiac output is distributed to the skeleton. When the model was perturbed to simulate changes in systemic or skeletal blood flow, we found that the system behaves in a nonlinear manner; even a five-fold increase in systemic or skeletal blood flow did not appreciably increase the amount of fluoride taken up by bone 1--2 hr later, the time when scans are usually made. A simulated increase in bone extraction rate, however, had a marked effect on bone-fluoride uptake. These findings suggest an important homeostatic role for bone in the regulation of blood calcium concentration and have considerable bearing on the interpretation of bone scans.

Soft-tissue uptake of technetium-99m-MDP after prostate cryoablation.

Prominent soft-tissue uptake of 99mTc-methylene diphosphonate (MDP) within the prostate bed was found after cryoablation for prostate carcinoma. CT, MRI and sonographic studies demonstrated liquifactive necrosis of the prostate bed. The probable etiology for 99mTc-MDP uptake in this case is necrosis with subsequent neovascular hyperemia and microscopic calcium deposits. Three-phase scintigraphy with 99mTc-MDP appears to be useful for localizing the extent of soft tissue inflammation and necrosis.

Studies of skeletal tracer kinetics. III. Tc-99m(Sn)methylenediphosphonate uptake in the canine tibia as a function of blood flow.

Experiments were performed in 14 dogs to study the effect of changes in bone blood flow on the tibial uptake of the skeletal tracer Tc-99m(Sn)methylenediphosphonate (Tc-99m MDP). Aortic blood was diverted through a pulsatile-flow pump in order to monitor and control femoral arterial blood flow. Tibial nutrient perfusion, as measured with labeled microspheres, paralleled the changes in arterial flow. We found that increments in bone blood flow up to four times normal produced only minimal augmentation of Tc-99m MDP uptake (mean = 33%), a markedly nonproportional relationship. The data points clustered about a predicted curve produced by perturbing the rate constants of a seven-compartment model obtained in normal dogs. These findings indicate that bone uptake of Tc-99m MDP is diffusion-limited, and they therefore cast doubt upon the validity of a method used for many years for estimating bone blood flow, the so-called skeletal tracer clearance technique. Nerve section, performed in 14 other dogs, augmented Tc-99m MDP uptake by about 50% at supranormal flows, suggesting a parallel-flow model of the microcirculation in bone, under sympathetic control. Such a model satisfactorily explains many scintigraphic findings in disease states.

Comparison of left anterior oblique and geometric mean gastric emptying.

A left anterior oblique image (LAO) and the geometric mean of anterior and posterior counts have both been proposed as methods for acquiring gastric emptying data. Both approaches are used to correct for the changes in attenuation that occur as the depth of radiolabeled solids changes during gastric emptying. These two methods were compared by using a power exponential curve fit to calculate a lag phase, an equilibrium emptying rate, and a half-time for gastric emptying in 20 patients. There were no significant differences (mean +/- 1 s.e.m.) in the measured half-emptying time (115 +/- 10 versus 104 +/- 7 min) (p = 0.08) or rate of gastric emptying (0.015 +/- 0.002 versus 0.015 +/- 0.002 min-1) (p = 0.56) for LAO imaging versus the geometric mean. However, the LAO measurements of the lag phase were significantly higher (69 +/- 7 min) than the geometric mean (53 +/- 6 min) measurements (p = 0.004). This resulted in 4/20 (20%) of patients with normal geometric mean lag phase measurements who would have been reclassified as abnormal using the LAO method.

The mode of action alginic acid compound in the reduction of gastroesophageal reflux.

This study was designed to evaluate quantitatively the mode of action of alginic acid compound (AAC) in the treatment of patients with symptomatic gastroesophageal reflux. Gastroesophageal scintigraphy using an orall administered Tc-99m sulfur colloid solution was used to demonstrate that AAC decreased significantly the gastroesophageal reflux index from (9.9 +/- 1.3) % to (6.5 +/- 0.8) % (p less than 0.05). No alteration of lower esophageal sphincter pressure was observed. After ACC was suitably labeled with Sr-87m, a dual-nuclide scintigraphic technique was used to show that most (greater than 75%) of the AAC was located in the upper half of the stomach in both normal subjects and patients with gastroesophageal reflux. In those subjects in whom reflux did occur after treatment with AAC, the Sr-87m-AAC refluxed into the esophagus preferentially compared with the liquid containing Tc-99m sulfur colloid. These findings suggest that AAC dimishes gastroesophageal reflux by means of its foaming, floating, and viscous properties.

Characterization of gastric antral motility disturbances in diabetes using a scintigraphic technique.

In this study, food distribution in the stomach and gastric antral motor activity in patients with longstanding diabetes have been evaluated. With use of a standard gastric emptying test with an acquisition protocol and a refined Fourier algorithm to analyze the data, antral contractions have been characterized and gastric motility parameters were correlated to gastric retention in 20 diabetic patients with or without gastroparesis and in 10 healthy subjects. The results of this study show that, in longstanding diabetes, gastric emptying retardation is accounted for by a retention of food in the proximal stomach, which is reflected by a prolonged lag phase as well as by a reduction in antral motor activity that is determined by a decrease in the amplitude of the antral contractions. This study demonstrates that scintigraphy can noninvasively characterize abnormalities of food distribution in the stomach and provides information similar to that obtained from manometry.

Dynamic antral scintigraphy to characterize gastric antral motility in functional dyspepsia.

UNLABELLED: We evaluated intragastric food distribution and antral motor activity in patients with functional dyspepsia. METHODS: A standard gastric emptying test and dynamic imaging of the antrum were used to characterize gastric antral motility disturbances and to correlate them with total and compartmental gastric emptying in 25 dyspeptic patients. RESULTS: We found a 40% prevalence of gastroparesis in functional dyspepsia. Solid gastric emptying delay is indicated by a prolonged lag phase and an increase in frequency and amplitude of gastric contractions, resulting in nonexpulsive antral contractions and/or antropyloric dyscoordination. Food retention in the distal stomach and antral distention appears to account for patients' dyspeptic symptoms. CONCLUSION: This study demonstrates that scintigraphy not only detects abnormalities of food distribution in the stomach but also provides information on antral motor activity noninvasively. Dynamic antral scintigraphy and compartmental gastric emptying are useful tools to define the pathophysiology of dyspeptic patients with or without gastroparesis.

The MIRD perspective 1999. Medical Internal Radiation Dose Committee.

The MIRD schema is a general approach for medical internal radiation dosimetry. Although the schema has traditionally been used for organ dosimetry, it is also applicable to dosimetry at the suborgan, voxel, multicellular and cellular levels. The MIRD pamphlets that follow in this issue and in coming issues, as well as the recent monograph on cellular dosimetry, demonstrate the flexibility of this approach. Furthermore, these pamphlets provide new tools for radionuclide dosimetry applications, including the dynamic bladder model, S values for small structures within the brain (i.e., suborgan dosimetry), voxel S values for constructing three-dimensional dose distributions and dose-volume histograms and techniques for acquiring quantitative distribution and pharmacokinetic data.

MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee.

The availability of quantitative three-dimensional in vivo data on radionuclide distributions within the body makes it possible to calculate the corresponding nonuniform distribution of radiation absorbed dose in body organs and tissues. This pamphlet emphasizes the utility of the MIRD schema for such calculations through the use of radionuclide S values defined at the voxel level. The use of both dose point-kernels and Monte Carlo simulation methods is also discussed. PET and SPECT imaging can provide quantitative activity data in voxels of several millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained using present imaging technology. For submillimeter dimensions, autoradiographic methods may be used when tissues are obtained through biopsy or autopsy. Sample S value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm on edge are given in the appendices to this pamphlet. These S values may be used to construct three-dimensional dose profiles for nonuniform distributions of radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data are also tabulated for 131I in 0.1-mm voxels for use in autoradiography. Two examples illustrating the use of voxel S values are given, followed by a discussion of the use of three-dimensional dose distributions in understanding and predicting biologic response.

Recent advances in gastric emptying scintigraphy.

Gastric emptying scintigraphy was introduced more than 25 years ago by Griffith and still remains the gold standard to assess gastric emptying. Test meals, radiopharmaceutical and acquisition procedures have been refined and optimized over the years and the test procedure is now well standardized. However, in its most common use, gastric emptying scintigraphy provides little information on gastric physiology and pathophysiology. Over the last decade, modeling of the liquid- and solid-emptying curves has provided some insight into the complex gastric physiology. Compartmental analysis of the stomach has also provided information on the pathophysiological mechanisms of delayed gastric emptying. Over the past 5 years, the most dramatic development in gastric emptying scintigraphy has been the introduction of digital antral scintigraphy. Digital antral scintigraphy consists primarily of dynamic imaging of the stomach and a refined Fourier transform processing method. This new procedure allows for the visualization of antral contractions and, like manometry, permits quantitative characterization of the frequency and amplitude of these contractions. Overall, this new procedure provides a unique, noninvasive tool to characterize gastric motility, to define the pathophysiological mechanisms of gastric motor disorders, and to evaluate the effect of new gastrokinetic compounds.

Ultrasound evaluation of the thyroid.

Ultrasound provides a safe noninvasive means of imaging the thyroid gland. It affords a reliable method of distinguishing cystic masses from other types of hypofunctioning thyroid nodules that might require surgical exploration. Due to the reported small frequency of false positive ultrasonic diagnoses (i.e., solid or complex masses being misdiagnosed as cysts), all cystic masses should be confirmed by aspiration. With gray-scale two-dimensional imaging, high-frequency transducers, and careful attention to technique, a reduction in the number of incorrect diagnoses can be expected.

Quantitation of regional ventilation during the washout phase of lung scintigraphy: measurement in patients with severe COPD before and after bilateral lung volume reduction surgery.

STUDY OBJECTIVES: We sought to investigate the effect of lung volume reduction surgery (LVRS) on regional lung ventilation. DESIGN: Retrospective analysis of routinely acquired data before and after LVRS. SETTING: Large, urban, university medical center. PATIENTS: Twenty-nine patients with severe emphysema. INTERVENTION: Bilateral LVRS. MEASUREMENTS AND RESULTS: (133)Xe washout curves during lung scintigraphy exhibit a biphasic pattern (the first component of the washout curve [m(r)] corresponds to an initial rapid phase in washout that reflects larger airways emptying, and the second component [m(s)] reflects a slower phase of washout that is attributed to gas elimination via smaller airways). We analyzed six standardized regions of the lung (upper, mid, and lower zones of the right and left lung), and calculated m(r) and m(s) for each lung region. The mean (+/- SE) baseline FEV(1) was 0.69+/-0.04 L, total lung capacity (TLC) was 139 +/-4% predicted, and the residual volume (RV)/TLC ratio was 65+/-2%. The mean improvement in FEV(1) 3 months post-LVRS was 38%. Post-LVRS, m(r) and m(s) increased in 79 and 74 lung regions, respectively, and there was no relationship with respect to lung regions that had or had not been operated on. The increase in m(s), however, significantly correlated with the increase in FEV(1) (r = 0.66; p<0.0001) and the decrease in RV/TLC (r = -0.67; p<0.0001). An increase in m(s) also correlated with a decrease in PaCO(2) (r = -0.39; p = 0.03), but m(r) showed no relationship with any parameter. CONCLUSIONS: Small airways ventilation in lung regions that had and had not been operated on is associated with a greater improvement in lung mechanics following LVRS.

The many causes of subclinical hyperthyroidism.

Subclinical hyperthyroidism, defined as serum thyroid hormone levels in the reference range with low serum TSH concentration, is a well recognized clinical entity, but little information is available concerning the prevalence of the disorders that produce it. We conducted a 24-month retrospective survey of subclinical hyperthyroidism patients referred to a university hospital nuclear medicine service for diagnostic studies. Twenty-four consecutive patients were evaluated (22 outpatients and 2 inpatients). All patients had highly sensitive TSH determination, thyroid hormone levels, radioiodine uptake and scan (except for 2 postpartum women), and, selectively, TSH-receptor antibody (TRAb), serum thyroglobulin, antithyroid antibodies, T3-suppression test, and erythrocyte sedimentation rate. A TSH value of about 0.1 microIU/mL was used as the cutoff. Only one patient in the group had a nonthyroidal disorder. In 14 patients (61%) subclinical hyperthyroidism was self-limited, due to silent thyroiditis (5 patients), iodine-induced hyperthyroidism (3 patients), postpartum thyroiditis (2 patients), subacute thyroiditis (2 patients), and probable hemorrhage into a functioning nodule (2 patients). Of the non-self-limited disorders (39%), Graves' disease accounted for 6 patients and solitary or multinodular goiter for 3. Graves' disease proved difficult to diagnose because the thyroid gland was normal in size in two of the six patients, TRAb was positive in only two of six, and the radioiodine uptake and gradient were normal in all six; the T3-suppression test was positive in two of two patients. We conclude that the causes of subclinical hyperthyroidism are the disorders that commonly produce overt thyrotoxicosis in medical practice, Graves' disease being the most frequent. However, the tests used to diagnose overt Graves' disease often fail in the setting of subclinical hyperthyroidism, except possibly the T3-suppression test.

Physiological significance of the rate constants in compartmental analysis.

Transfer (rate) constants in compartmental analysis are generally considered solely in operational terms, and little attention has been paid to their physiological interpretation. In this study we have examined the significance of their roles in physiological terms and the implications of this interpretation. When freely diffusible tracers are introduced into the blood stream by bolus injection, the sum of the exit rate constants from the blood compartment gives the number of blood volumes turned over per unit time; when multiplied by the blood volume, this value is the cardiac output. When corrected for body weight, the product yields the cardiac index, a biological constant for large mammals. The ratio of the rate constant supplying an organ to the exit-constant sum gives fractional cardiac output, and when multiplied by the cardiac output the ratio gives organ blood flow, independent of diffusibility. For freely diffusible tracers, organ blood flow can be calculated directly from the product of the organ rate constant and blood volume. At equilibrium and at equal concentration, the ratio of rate constants between adjacent compartments gives their relative volumes; this interpretation is fundamental when partitioning compartments for detailed analysis. These considerations have been validated by testing in both animals and man. Multiple solution sets may occur in mammillary models. Knowledge of the physiological interpretation of intercompartmental rate constants is of importance not only in model interpretation but in model validation, where this information serves as an independent check on model structure and its realization.