Use of radiologic modalities in coccidioidal meningitis.

The diagnostic utility of pentetate indium trisodium in 111 CSF studies, technetium Tc 99m brain scans, and computerized tomographic (CT) scans was evaluated in eight patients in whom coccidioidal meningitis developed following a dust storm in the Central Valley of California. The 111In flow studies and the CT scans demonstrated hydrocephalus in five patients with clinical findings suggesting this complication. Ventriculitis has not previously been diagnosed before death in patients with coccidioidal meningitis; however, it was demonstrated in two patients by the technetium Tc 99m brain scan. Basal meningitis, which is indicative of fungal infection, is also detectable on contrast-enhanced CT scan. The finding that communicating hydrocephalus occurs early in meningitis and interferes with CSF flow into infected basilar regions has important therapeutic implications in that antifungal agents injected into the lumbar subarachnoid space may not reach these regions.

Suprarenal abscess in the neonate: a case report and review of diagnosis and management.

A case of unilateral suprarenal abscess is reported. This is the third such reported case, and the first reported case successfully treated with preservation of the kidney. Diagnosis and treatment were aided significantly by a thorough preoperative radiological evaluation, including angiography.

Thrombotic complications of umbilical artery catheters: A clinical and radiographic study.

Catheterization of the aorta via the umbilical artery provides a convenient route for monitoring arterial blood pressure, for obtaining blood specimens for measurement of blood gas tensions and chemistries, and for the infusion of fluids and pharmacologic preparations in sick newborn infants. Use of this technique may be accompanied by a number of complications of which thrombotic phenomena are the most common. Twenty-three of 98 (24%) newborn infants undergoing umbilical artery catheterization were found to have thrombotic complication determined by aortography. No correlation was present between the duration of time that the umbilical artery catheters were in place and the occurrence of thrombotic complications. From paired aortographic or aortographic and autopsy studies in 24 patients, it was concluded that if a thrombotic complication did not occur early, none was likely to occur subsequently. One patient was considered to have died as a direct result of a thrombotic complication. Aortography is a safe, simple, and reliable technique for the early detection of thrombotic complications of umbilical artery catheters. Umbilical artery catheterization is not without risk and careful selection of patients for this procedure is indicated.

Postprandial gastric motility in infants with gastroesophageal reflux and delayed gastric emptying.

Delayed gastric emptying of formula is observed in many infants with gastroesophageal reflux but the mechanisms responsible for this observation are not defined. Postprandial gastric motility was quantified using a perfused catheter placed into the distal stomach of five infants with gastroesophageal reflux and delayed gastric emptying of 99mTc-sulfur colloid-labeled formula. Five infants with reflux who exhibited normal emptying of formula served as the controls. Gastric motility indices were calculated for 60 min following a meal. Half the patients in each group were given metoclopramide following a 30-min recording period. In both groups, postprandial gastric motility was similar and characterized by minimal gastric contractions. Metoclopramide resulted in increased amplitude and duration of antral contractions, but no significant differences were noted between groups. The findings suggest that minimal delays in gastric emptying in infants with gastroesophageal reflux are not associated with significant alterations of postprandial gastric motility.

Validation of in vivo receptor measurements via in vitro radioassay: technetium-99m-galactosyl-neoglycoalbumin as prototype model.

Hepatic binding protein (HBP) is a hepatocyte-specific receptor for serum asialoglycoproteins. The receptor also recognizes a synthetic glycoprotein that has been developed as a radiopharmaceutical, technetium-99m-galactosyl-neoglycoalbumin (99mTc-NGA). This report describes the correlation between receptor parameters measured in vivo via kinetic modeling of 99mTc-NGA and those measured by in vitro radioassay of biopsied liver tissue. Eleven patients with diffuse hepatic disease underwent percutaneous liver biopsy followed by a 99mTc-NGA functional imaging study. In vivo measurements of HBP quantity Ro and forward binding rate constant kb obtained from the kinetic analysis of 99mTc-NGA liver and blood time-activity data were compared to total receptor quantity and the HBP-99mTc-NGA association constant KA as measured by Scatchard binding assay of the biopsied tissue. The correlation coefficients between in vivo and in vitro measurements were 0.73 (df = 8, p = 0.015) and 0.98 (df = 8, p less than 0.01) for Ro and kb, respectively. The in vivo measurements of HBP biochemistry via kinetic analysis of the radiopharmaceutical time-activity data reflect the average concentration and affinity of the receptor. This study further substantiates the validity of 99mTc-NGA as a quantitative probe for the HBP receptor.

Kinetic sensitivity of a receptor-binding radiopharmaceutical: technetium-99m galactosyl-neoglycoalbumin.

Kinetic sensitivity is the ability of a physiochemical parameter to alter the time-activity curve of a radiotracer. The kinetic sensitivity of liver and blood time-activity data resulting from a single bolus injection of [99mTc]galactosyl-neoglycoalbumin [( Tc]NGA) into healthy pigs was examined. Three parameters, hepatic plasma flow scaled as flow per plasma volume, ligand-receptor affinity, and total receptor concentration, were tested using [Tc]NGA injections of various molar doses and affinities. Simultaneous measurements of plasma volume (iodine-125 human serum albumin dilution), and hepatic plasma flow (indocyanine green extraction) were performed during 12 [Tc]NGA studies. Paired data sets demonstrated differences (P(chi v2) less than 0.01) in liver and blood time-activity curves in response to changes in each of the tested parameters. We conclude that the [Tc]NGA radiopharmacokinetic system is therefore sensitive to hepatic plasma flow, ligand-receptor affinity, and receptor concentration. In vivo demonstration of kinetic sensitivity permits delineation of the physiologic parameters that determine the biodistribution of a radiopharmaceutical. This delineation is a prerequisite to a valid analytic assessment of receptor biochemistry via kinetic modeling.

Sentinel node imaging via a nonparticulate receptor-binding radiotracer.

UNLABELLED: Technetium-99m-labeled polydiethylenetriamine pentaacetic acid polymannosyl polylysine (DTPA-man-PL) was synthesized and tested for lymph node scintigraphy by subcutaneous administration. The agent was designed for receptor-mediated uptake by mannosebinding protein, which resides on the plasma membrane of reticuloendothelial cells. METHODS: Subcutaneous injections of a 99mTc-labeled agent having 18 DTPA and 82 mannosyl groups attached to a polylysine of 100 units ([99mTc]DTPA18-man82-PL100) were made at the level of the metacarpus and metatarsus of three healthy rabbits. Images were acquired at 1, 6, 12 and 24 hr. Popliteal and axillary nodes were then assayed for percent of injected dose (%ID). A negative control study was performed in three normal rabbits with [99mTc]DTPA18-PL100. RESULTS: Significant differences in mean 24-hr %ID between the receptor specific and nonspecific agents were observed for both the popliteal (p < 0.006) and axillary (p < 0.012) nodes. Popliteal percent injected dose at 24 hr was 3.00 +/- 0.72% for [99mTc]DTPA-man-PL and 0.13 +/- 0.08% for [99mTc] DTPA-polylysine. Axillary accumulation at 24 hr was 2.84 +/- 0.83% for [99mTc]DTPA-mannosyl-polylysine and 0.22 +/- 0.12% for [99mTc] DTPA-polylysine. Percent injected dose of the receptor-specific agent was highest (4%) during the 6-hr scan. Accumulation of the nonspecific agent by the popliteal and axillary nodes at 6-hr postinjection was approximately 0.5%. CONCLUSION: This study provides proof of principle for lymphoscintigraphy by receptor-mediated delivery of a nonparticulate imaging agent.

Automatic preparation of radiopharmacokinetic data for in vivo estimation of receptor biochemistry.

UNLABELLED: We present a fully automated region of interest (ROI) and motion correction program for the generation of heart and liver time-activity data resulting from a hepatic functional imaging study using [99mTc-]galactosyl-neoglycoalbumin (99mTc-NGA). METHODS: The program automatically draws heart and liver ROI and corrects for lateral movement of the subject. Eighty-four 99mTc-NGA studies, consisting of 32 healthy subjects and 52 patients with liver disease, were processed and submitted to an automated kinetic analysis that estimates the subject's asialoglycoprotein receptor concentration [R]o. RESULTS: When compared to time-activity data generated by operator-drawn ROIs without motion correction, the average reduced Chi-square of the kinetic analysis decreased significantly (p < 0.001) from 2.20 to 1.37 and the number of studies that satisfied quality control increased from 74 to 81 studies. Receiver operating characteristic of [R]o resulted in greater detectability (0.984 +/- 0.012 compared with 0.965 +/- 0.020) when automatic ROI generation was employed. Using the test criteria of 0.65 microM, the sensitivity of [R]o increased from 0.88 to 0.92 and the specificity increased from 0.96 to 0.97. CONCLUSION: Automated definition of liver and heart ROIs with motion correction, that reduces observational noise, increased the success rate of the radiopharmacokinetic analysis from 88% to 96%.

Critical evaluation of hepatic scintiangiography for neoplastic tumors of the liver.

Dynamic hepatic scintiangiography increases the specificity of diagnosis of space-occupying lesions of the liver seen on hepatic scintigraphy. The purpose of this study was to evaluate and compare critically this procedure with histologic and radiopaque diagnosis in the evaluation of suspected hepatic neoplasms. Ninety-two patients had hepatic scintiangiography, scintigraphy, and histologic certification. In ten of these patients the findings of radiopaque arteriography were compared with those of hepatic scintiangiography. In all ten patients with hepatoma, the scintiangiographic and histologic observations correlated; nine of these ten patients had a "tumor stain." Fifty-one of 59 patients with metastases to the liver had scinitangiograms that showed "tumor stain." In 2 of these 59 patients, scintiangiography revealed tumor vascularity whereas the results of scintigraphy were normal. In two of four patients with metastases and two of six patients with hepatomas, scintiangiograms revealed "tumor stain" that was not evident on radiopaque afteriography. Conclusions from this study are: (A) neoplastic arterialization or "tumor stain" is more readily detected by scintiangiography than by radiopaque arteriography; (B) a normal scintigram and a "tumor stain" on the scintiangiogram in a patient with a known primary neoplasm outside the liver is suggestive of hepatic metastases; and (C) a normal scintigram and scintiangiogram make neoplastic involvement of the liver improbable. Dynamic hepatic scintiangiography is a simple, clinically useful method for increasing the specificity of diagnosis of diagnosis of space-occupying lesions of the liver and should be part of the evaluation for possible neoplastic involvement.

Technetium-99m galactosyl-neoglycoalbumin: preparation and preclinical studies.

Technetium-99m galactosyl-neoglycoalbumin ([Tc] NGA), a labeled analog ligand to the hepatocyte-specific receptor, hepatic binding protein (HBP), was prepared and tested for labeling yield, stability, biodistribution, toxicity, and dosimetry. The ligand was synthesized by the covalent coupling of a carbohydrate bifunctional reagent, 2-imino-2-ethyloxymethyl-1-thiogalactose, to human serum albumin. Testing in mice and rabbits revealed the product to be nontoxic and apyrogenic. Technetium labeling yields in excess of 95%, by the electrolytic method, did not alter the molecular weight profile of the neoglycoalbumin. The NGA-bound activity remained stable for at least 4 hr. Biodistribution studies in rabbits demonstrated the liver as the single focus of tracer uptake. Dosimetry was based on kinetic studies in three baboons. Absorbed doses to liver, small intestine, urinary bladder wall, and uterus were 0.089, 0.28, 0.56, and 0.88 rad/mCi, respectively. Total body, lens of the eye, red marrow, ovaries, and testes were less than 0.06 rad/mCi. High liver specificity imparted by receptor binding combined with high labeling yield, stability, acceptable dosimetry, and safety provide [Tc]NGA with the attributes required for routine clinical assessment of hepatocyte function.

Diagnostic performance of a receptor-binding radiopharmacokinetic model.

UNLABELLED: The aim of this study was to determine which measurement obtained from a radiopharmacokinetic model of a receptor-binding radiotracer provides the highest diagnostic performance for the detection of diffuse hepatocellular disease. METHODS: Twenty-seven healthy subjects and 46 patients with diffuse hepatocellular disease were studied with the receptor-binding radiopharmaceutical, 99mTc-galactosyl-neoglycoalbumin. A radiopharmacokinetic model was used to produce estimates of receptor concentration [R]o, the scaled forward-binding rate constant Kb, hepatic plasma volume, Vh, extrahepatic plasma volume, Ve and hepatic plasma flow, F. Receiver operating characteristic analysis of each model estimate was conducted. RESULTS: Receptor concentration [R]o and the metrics [R]o/tbw and kb[R]o[R]o/tbw provided the best discrimination between healthy and diseased liver. The forward-binding rate constant kb and the metrics F/Ve and Vh/tbw provided no discrimination. CONCLUSION: Based on simplicity and higher measurement precision, [R]o was selected as the most accurate index of hepatic function.

Measurement of receptor concentration and forward-binding rate constant via radiopharmacokinetic modeling of technetium-99m-galactosyl-neoglycoalbumin.

Technetium-99m-galactosyl-neoglycoalbumin (99mTc-NGA) is a synthetic ligand to the hepatocyte receptor, hepatic binding protein (HBP). A five-state mathematical model containing a bimolecular chemical reaction was utilized for quantitative estimation of the following physiologic and biochemical parameters: extrahepatic plasma volume Ve; hepatic plasma flow F and volume Vh; receptor-ligand forward-binding rate constant kb and reaction volume Vr; and receptor concentration [R]o. Nine normal subjects were studied. Given (a) liver and heart time-activity data, (b) the patient's weight, height, and hematocrit, (c) the fraction of injected dose in a 3-min blood sample, and (d) the amount and galactose density of the NGA dose, a computer program executed a curve-fit to the kinetic model. Systematic error, as measured by reduced chi-square, ranged from 1.43 to 2.56. Based on the nine imaging studies, the mean and relative error of each parameter were: [R]o, 0.813 +/- (0.11) microM; kb, 2.25 +/- (0.15) microM-1 min-1; F, 0.896 +/- (0.20) liter/min; Ve, 1.67 +/- (0.27) liter; and Vh, 0.228 +/- (0.22) liter. Two unique features of 99mTc-NGA radiopharmacokinetic systems permit the simultaneous estimates of receptor quantity, ligand affinity, and hepatic plasma flow. The first is the ability to administer a quantity of ligand capable of occupying a significant fraction of receptor; and the second is a simple model structure that conserves mass.

Recovery of hepatic asialoglycoprotein receptors after major hepatic resection.

UNLABELLED: Although morphological restoration of the hepatic mass after partial hepatectomy has been well studied, fewer reports have appeared on the change of functional hepatic capacity during liver regeneration. Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoprotein. Kinetic modeling of 99mTc-labeled diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (TcGSA) time-activity data yields estimates of ASGP-R concentration [R]o and amount R0, which are directly related to functional liver mass. We have investigated the changes in ASGP-R status as well as liver volume in regenerating human liver after major hepatic resection. METHODS: Twenty-two patients (18 noncirrhotic, 4 cirrhotic) had a TcGSA study before and 3 wk after major hepatic resection, with a mean hepatic parenchymal resection rate of 36.0%. RESULTS: [R]0 was significantly decreased from 0.683+/-0.024 micromol/L to 0.565+/-0.032 micromol/L (P < 0.001) after resection. The decrease in [R]0 was more prominent in cirrhotic patients. Recovery of ASGP-R was observed as a significantly increased R0 3 wk after the operation. Subsequent (long-term) restoration of ASGP-R appeared to be slower when compared with the volume restoration. CONCLUSION: ASGP-R concentration of the liver significantly decreased after major hepatic resection. Subsequent recovery of ASGP-R amount was shown by TcGSA study. By estimating hepatic functional reserve expressed by ASGP-R amount and concentration, one may detect a delayed or impaired liver regeneration with higher sensitivity.

Catabolism and protein binding of Tc-99m pyridoxylideneglutamate.

Various Tc-99m-labeled compounds have been suggested as replacements for [I-131] rose bengal for imaging of the hepatobiliary system. Among such compounds are Schiff's bases, which are tin-free Tc-chelates easily prepared by 30-min autoclaving of an equimolar mixture of pyridoxal and an amino acid at pH 8.5. We have compared the properties of several Schiff's bases, including Tc-99m pyridoxylideneglutamate (Tc PyG) with [I-131] rose bengal. Under conditions described, Tc-PyG can be prepared free of Tc-pyridoxal and with less than 2% TcO4- radiochemical impurity. Blood clearance and biliary excretion were studied in three animal models, and in normal human volunteers. In all animal models, Tc-PyG initially cleared from the blood more rapidly than rose bengal, but a significant amount of Tc-PyG was excreted in the urine, this in contrast to [I-131] rose bengal which was almost completely excreted through the biliary system. Species differences were observed in the degree of urinary versus biliary clearance of Tc-PyG, with significantly greater urinary excretion in dogs than in monkeys and rabbits. Replacing glutamate with other amino acids did not significantly increase the blood clearance rate or decrease urinary excretion, so that Tc-PyG appears to be at least as good as any of the others studied. Tc-PyG was only 20% bound to plasma proteins, and electrophoretic and chromatographic studies did not reveal any in vivo changes of Tc-PyG before excretion in urine or bile.

Scintigraphic imaging of a blind-ending ureteral duplication.

The scintigraphic image is compared with the urographic appearance of blind-ending ureteral duplication.

Tc-99m galactosyl-neoglycoalbumin: in vitro characterization of receptor-mediated binding.

Hepatic binding protein (HBP) is a membrane receptor that binds and transports plasma glycoproteins from hepatic blood to hepatocellular lysosomes. We have characterized the in vitro binding of Tc-99m galactosyl-neoglycoalbumin (Tc-NGA), a synthetic HBP ligand, to liver membrane. Structural modifications of NGA resulted in the alteration of the equilibrium constant, KA, and the forward-binding rate constant, kb. Binding was second-order; the relative amount of membrane-bound NGA depended on the initial concentrations of ligand and membrane. Membrane displacement studies, using carrier ligands in contrast to previously bound Tc-NGA or I-NGA, correlated with the binding characteristics of a native HBP ligand, asialo-orosomucoid. We used computer simulation to study the detectability of the changes in HBP concentration at different values of kb. The simulations indicated that radiopharmacokinetic sensitivity to alterations in [HBP] should be possible using a neoglycoalbumin preparation with a carbohydrate density within the range of 15 to 25 galactose units per albumin molecule.

Renal clearance and extraction parameters of ortho-iodohippurate (I-123) compared with OIH(I-131) and PAH.

o-[131I] iodohippurate [OIH(I-131)] has been used for many years in the estimation of effective renal plasma flow. This compound suffers from low photon yield and poor images when the quantity used is limited to stay within a reasonable radiation dose. To test the validity of substituting I-123 for I-131, a series of experiments was performed in a surgically prepared dog model. The extraction ratios and clearance values OIH(I-123) prepared from radionuclidically pure I-123 were compared with those of commercial OIH(I-131) and PAH. The extraction ratios for OIH(I-123) and OIH(I-131) were 0.65 and 0.67, representing 0.86 and 0.88 that of PAH, respectively. The clearance values (cc/min/kg) for the I123 and I-123) can be used to estimate effective renal plasma flow; moreover, because of the high yield within an acceptable radiation dose range, images of good quality can be produced.

Technetium-99m NGA functional hepatic imaging: preliminary clinical experience.

Technetium-99m galactosyl-neoglycoalbumin ( [Tc]NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis (two had concurrent hepatoma and one chronic active hepatitis), and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and [Tc]sulfur colloid scintigraphy. Kinetic modeling of dynamic [Tc]NGA data produced estimates of standardized hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, [HBP]. Clinical correlation was by classical Child-Turcotte criteria (CTC). Significant rank correlation was obtained between [HBP] estimates and CTC scores (rs = -0.72, p = 0.001). This correlation supports the hypothesis that [HBP] is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced [HBP] may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging.

A musculoskeletal radiologist's view of nuclear medicine.

The introduction of cross-sectional and multiplanar imaging techniques has not diminished the value of radionuclide bone scanning. Skeletal scintigraphy remains an extremely effective and relatively inexpensive tool for diagnosis of many disorders of bones and joints. The sensitivity of scintigraphy in detecting stress fractures approaches 100%, although it is less specific than plain film radiography. However, radionuclide bone scanning can reveal subtle early changes in bone metabolism. For evaluation of infections, particularly in patients with diabetic foot neuropathy, scintigraphy is the modality of choice, although a combination of imaging techniques may be necessary in previously damaged bone. Radionuclide bone scanning has retained its place in the evaluation of primary bone tumors and metastases, and in screening of patients with metabolic bone disease. The radiologist should be aware that although this modality is generally used as an ancillary technique in conjunction with plain radiography, conventional tomography, computed tomography (CT), and magnetic resonance imaging (MRI), at times it can be used as the primary modality not only for the identification of skeletal lesions but also to provide important information required to make a definite diagnosis.

Tc-NGA imaging in liver transplantation: preclinical studies.

Tc-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver-imaging agent which binds to hepatic binding protein (an hepatocyte-specific membrane receptor). This study evaluated the sensitivity of Tc-NGA kinetics and imaging anatomy to pathologic states that are encountered after liver transplantation. Studies were performed in adolescent pigs under control conditions (18 studies), and after orthotopic liver transplantation (nine studies), common bile duct ligation (three studies), hepatic artery ligation (one study), and hepatic resection (two studies). Anatomic and kinetic data were analyzed. Excellent liver images and minimal kinetic changes were noted after common bile duct ligation. Marked imaging defects and major kinetic alterations were observed after hepatic artery ligation and in the presence of preservation injury. Marked depression in hepatic Tc-NGA uptake was observed during acute rejection. Minor alterations in Tc-NGA kinetics were noted after a 25% hepatectomy. These studies indicate that minimal changes in Tc-NGA uptake occur after common bile duct ligation; Tc-NGA uptake is markedly sensitive to hepatic ischemia; decreased Tc-NGA uptake occurs during acute rejection; and hepatic infarcts are demonstrated promptly after preservation injury. Thus Tc-NGA imaging provides a novel means of evaluating hepatic ischemia, hepatic preservation, and hepatic allograft rejection. Tc-NGA imaging may also provide a means of evaluating hepatic regeneration and hepatocyte retrodifferentiation during regeneration.