Evaluation of Tc-99m pyridoxal-phenylalanine as a hepatobiliary agent. Part 2. Clinical tests

Twenty-four patients with normal or diseased hepatobiliary systems were subjected to a clinical trial in order to evaluate Tc-99m pyridoxal-phenylalanine as a biliary imaging agent. The investigation was combined with i.v. cholecysto-cholangiography in most cases, and the results were compared. It is concluded that qualitative information derived from conventional i.v. cholangiography is better in demonstrating the normal biliary tree or gallstones. The radiotracer techniques, however, are valuable in dynamic studies of Oddi's sphincter, in showing patency of biliary by-pass procedures, and in differentiating hepatocellular from obstructive jaundice.     

Choledochal cyst: comparison of MR and conventional cholangiography

AIMS: To assess the diagnostic value of magnetic resonance (MR) cholangiography versus conventional cholangiography in patients with choledochal cyst and to determine whether MR cholangiography can be considered an alternative to conventional cholangiography. MATERIALS AND METHODS: Thirteen patients with choledochal cyst were examined by MR cholangiography and conventional cholangiograms. Magnetic resonance cholangiography employed T2-weighted axial and coronal fast spin-echo, single and multislab single-shot fast spin-echo sequences, including source images with maximum intensity projections. The diagnostic value of MR cholangiography and conventional cholangiograms was assessed and compared using the criteria of depiction of morphology, anomalous pancreaticobiliary duct union and demonstration of complications such as stones. A four-point diagnostic scale was applied to the delineation of the ductal anatomy with the Wilcoxon signed-ranks test and McNemar's test used for statistical analysis. RESULTS: The depiction of the choledochal cyst was significantly better with MR cholangiography than with conventional cholangiography (P = 0.03). The detection rate of an anomalous pancreaticobiliary duct union was not significantly different with either method (P = 0.641), nor was the detection rate of bile duct stones (P = 0.375). CONCLUSION: Magnetic resonance cholangiography provides data equivalent to or superior to those from conventional cholangiography in evaluating choledochal cyst. Magnetic resonance cholangiography is recommended as a non-invasive examination of choice for the evaluation of choledochal cyst.     

Biliary tract depiction in living potential liver donors: comparison of conventional MR, mangafodipir trisodium-enhanced excretory MR, and multi-detector row CT cholangiography--initial experience

PURPOSE: To compare biliary tract depiction in living potential liver donors at conventional magnetic resonance (MR), mangafodipir trisodium-enhanced excretory MR, and multi-detector row computed tomographic (CT) cholangiography. MATERIALS AND METHODS: Eight living potential liver donors underwent iodipamide meglumine-enhanced CT cholangiography. Eight different potential liver donors then underwent conventional MR cholangiography and mangafodipir trisodium-enhanced excretory MR cholangiography. Two readers independently scored all first-, second-, and third-order biliary branches with a four-point scale from 0 (not seen) to 3 (excellent visualization). Interobserver agreement was calculated by using the weighted kappa statistic. Scores were compared between imaging modalities by using generalized estimating equations. Imaging findings of second-order biliary tract anatomy were compared with intraoperative findings for nine patients. RESULTS: Interobserver agreement for overall biliary tract visualization was good for CT, conventional MR, and excretory MR cholangiography (with weighted kappa values of 0.76, 0.66, and 0.79, respectively). The mean second-order biliary branch visualization scores for readers 1 and 2, respectively, were significantly higher at CT cholangiography (2.81 and 2.75) than at conventional MR (1.84 and 1.75, P <.001), excretory MR (2.00 and 2.06, P <.001), and combined conventional and excretory MR cholangiography (2.31 and 2.25, P <.01). At CT, conventional MR, and excretory MR cholangiography, respectively, second-order biliary branching anatomy was discernible in eight, five, and seven patients, with second-order biliary branch variants seen in three, two, and two patients. Surgical findings confirmed the pattern of second-order biliary branching seen at CT in five patients, that seen at conventional MR imaging in one patient, and that seen at excretory MR cholangiography in three patients. At surgery, one case of variant biliary anatomy was found to have been missed at CT cholangiography. CONCLUSION: In living potential liver donors, CT cholangiography enables significantly better biliary tract visualization than conventional or excretory MR cholangiography either alone or in combination.     

Biliary obstruction: findings at MR cholangiography and cross-sectional MR imaging.

Twenty-two patients with malignant biliary obstruction and 21 patients with suspected obstruction of biliary-enteric anastomoses were evaluated over a 12-month period with magnetic resonance (MR) cholangiography and cross-sectional MR imaging. In patients with malignant obstruction, MR cholangiography helped accurately determine the status of the biliary ductal system by identifying the exact location and extent of the obstruction and the severity of duct dilatation. In so doing, MR cholangiography helped determine whether percutaneous transhepatic cholangiography with antegrade stent placement or retrograde cholangiography with stent placement constituted the more suitable treatment. Cross-sectional MR imaging was necessary to identify the organ of tumor origin, define the tumor margins, and determine the stage of disease. This information helped evaluate the appropriateness of curative surgical therapy versus palliative drainage procedures. In patients with biliary-enteric anastomoses, MR cholangiography clearly depicted the site of the anastomosis and demonstrated the status of the intrahepatic ducts, thereby helping determine which patients would benefit from undergoing antegrade duct cannulation with a drainage procedure or perhaps balloon dilation. In some of these patients, MR cholangiography was sufficient to help plan therapeutic intervention. MR cholangiography also demonstrates the presence and size of biliary stones and associated findings such as intraductal tumor growth. In addition, MR cholangiography may obviate retrograde cholangiography, which can be technically difficult to perform.     

Cholescintigraphy in the diagnosis of intrahepatic cholestasis. How specific is it?

Previous results from tests on a limited number of patients suggested that the combination of relatively normal hepatocyte clearance, prolonged parenchymal transit time, and eventual passage of radiotracer into the intestine or gallbladder without evidence of biliary tract dilatation were relatively specific for intrahepatic cholestasis. We reevaluated the specificity of cholescintigraphy for the diagnosis of intrahepatic cholestasis in an unselected group of patients from a general hospital. Sixteen patients had the cholescintigraphic findings of intrahepatic cholestasis and an established diagnosis of biliary tract dilatation or nondilatation by ultrasound, ERCP, or intraoperative cholangiography. Using 6 mm as the upper limits of normal for the diameter of the common hepatic duct by ultrasonography resulted in a specificity of 63% (10 correct out of 16); using 6 mm plus 1 mm for for every decade over 60 years of age gave a specificity of 75% (12 correct out of 16); and using the more liberal criterion of 8 mm as the upper limits of normal increased the specificity to 81% (13 out of 16). The data suggest that cholescintigraphy alone is unreliable in differentiating intrahepatic cholestasis from extrahepatic obstruction, even when the obstruction is partial and radiotracer eventually passes through the extrahepatic biliary tract.     

Living donor candidates for right hepatic lobe transplantation: evaluation at CT cholangiography--initial experience

PURPOSE: To retrospectively evaluate computed tomographic (CT) cholangiography in the depiction of second-order biliary tract anatomy in living donor candidates for right hepatic lobe transplantation. MATERIALS AND METHODS: Human research committee approval was obtained, informed consent was not required, and the study was compliant with the Health Insurance Portability and Accountability Act. The authors identified all living right-lobe liver donor candidates who underwent CT cholangiography at their institution between October 2001 (when CT cholangiography was introduced at the institution) and March 2003 (n = 62). There were 41 men (mean age, 36 years; range, 18-55 years) and 21 women (mean age, 40 years; range, 22-55 years). Two readers in consensus rated quality of second-order bile duct visualization at CT cholangiography on a four-point scale (0, not seen; 3, excellent visualization) and noted the presence of variant second-order biliary tract branching anatomy. CT cholangiography findings were compared with those at surgery in subjects who underwent right hepatic lobe retrieval (n = 24). In addition, adult donors who underwent right hepatic lobe retrieval between January 2000 and March 2003 (29 men, mean age, 35 years [range, 20-52 years]; 18 women, mean age, 38 years [range, 23-54 years]) were identified. Numbers of donors who underwent intraoperative cholangiography before and after the introduction of CT cholangiography were compared by using the Fisher exact test. RESULTS: The mean second-order bile duct score at CT cholangiography was 2.9 (range, 2-3). Of 24 subjects who underwent right lobe retrieval, biliary tract anatomy determined at CT cholangiography was concordant with findings at surgery in 23 (96%). Variant second-order branching anatomy was seen in 13 subjects (54%) at surgery; one variant branch was missed at CT cholangiography. Of 47 subjects who underwent right hepatic lobe retrieval, significantly fewer subjects required conventional intraoperative cholangiography after the introduction of CT cholangiography (three of 24 subjects [12%]) than before (23 of 23 subjects; P < .0001). CONCLUSION: CT cholangiography accurately depicts biliary tract anatomy in living donor candidates for right hepatic lobe transplantation, and donors who undergo preoperative CT cholangiography are unlikely to need conventional intraoperative cholangiography.     

Intravenous computed tomographic cholangiography in acute cholecystitis. A comparison with conventional cholangiography

Forty-nine patients with clinical signs of acute cholecystitis underwent conventional and computed tomographic cholangiography. Among 39 patients with signs of contrast medium in the biliary system at both examinations there was a diagnostic discrepancy in only one patient. Conventional radiography demonstrated cholecystopathy in this patient while contrast medium in the gallbladder and an acute pancreatitis were found at computed tomography. Ten patients with an indeterminate conventional cholangiography had a conclusive computed tomographic examination. Twenty of 30 patients with an abnormal computed tomographic cholangiography underwent cholecystectomy and all had diseased gallbladders. All 17 patients with histopathologically confirmed acute cholecystitis had signs of subserosal edema and/or changes in the omental fatty tissue adjacent to the gallbladder at computed tomography. A layer of tissue of water-density adjacent to the gallbladder and/or changes in omental fatty tissue were also seen in one patient with congestive heart failure and in one with a penetrating duodenal ulcer. None of the 19 patients with a normal computed tomographic cholangiography had a proven acute cholecystitis.     

Using contrast-enhanced MR cholangiography with IV mangafodipir trisodium (Teslascan) to evaluate bile duct leaks after cholecystectomy: a prospective study of 11 patients

OBJECTIVE: The purpose of our study was to determine whether contrast-enhanced MR cholangiography using IV mangafodipir trisodium can accurately detect the presence and location of bile duct leaks in patients who have undergone cholecystectomy. SUBJECTS AND METHODS: Our study group included 11 patients with suspected bile duct leaks after cholecystectomy. Axial single-shot fast spin-echo and gradient-echo images were acquired in all patients before and 1-2 hr after IV administration of mangafodipir trisodium. The contrast-enhanced MR cholangiograms were evaluated for image quality, degree of ductal or small bowel opacification, and the presence and location of bile duct leaks, strictures, and stones. MR cholangiograms were correlated with conventional contrast-enhanced cholangiograms obtained in all patients, including endoscopic retrograde cholangiography (n = 10) and percutaneous transhepatic cholangiography (n = 1). RESULTS: Excretion of mangafodipir trisodium was noted in the intrahepatic and extrahepatic bile ducts in all patients from 1 to 2 hr after IV administration. Bile ducts and fluid collections that contained excreted mangafodipir trisodium showed increased signal intensity on gradient-echo sequences and decreased signal intensity on single-shot fast spin-echo sequences. Conventional contrast-enhanced cholangiography showed the presence of bile duct leaks in six patients and the absence of bile duct leaks in five patients, with false-negative findings in one patient and false-positive findings in one patient for bile duct leak (sensitivity, 86%; specificity, 83%). CONCLUSION: Contrast-enhanced MR cholangiography with IV mangafodipir trisodium can successfully detect the presence and location of bile duct leaks in patients suspected of having such leaks after undergoing cholecystectomy. More research is necessary before acceptance of this examination as routine in the workup of these patients.     

MR cholangiography and CT cholangiography of pediatric patients with choledochal cysts.

OBJECTIVE: We report our experience using MR cholangiography and CT cholangiography in pediatric patients with choledochal cysts. SUBJECTS AND METHODS: Fourteen patients (two boys, 12 girls; mean age, 7.8 years) with either a preoperative diagnosis of choledochal cyst or a surgical finding of choledochal cyst underwent non-breath-hold MR cholangiography using T2-weighted fat-suppressed fast spin-echo sequences with a 1.5-T magnet, and CT cholangiography with IV infusion of meglumine iodoxamic acid. Radiologic findings were correlated with findings from surgery, operative cholangiography, or percutaneous transhepatic cholangiography. RESULTS: The biliary tree was visualized in all 14 patients with MR cholangiography and in 13 patients (92.9%) with CT cholangiography. In the 11 preoperative cases of choledochal cyst, MR cholangiography correctly showed all cysts and CT cholangiography showed 10 cysts (90.9%). The quality of images on CT cholangiography and MR cholangiography was comparable. The sensitivity of CT cholangiography and MR cholangiography in revealing intrahepatic stones was 83.3% and 66.7%, respectively; the specificity for both techniques was 100%. The rate of detecting the pancreatic duct and the common channel by CT cholangiography and MR cholangiography was 63.6% and 45.5% respectively. After surgery, CT cholangiography was superior to MR cholangiography in revealing the location of biliary-enteric anastomosis and the extent of anastomotic narrowing. CONCLUSION: Because non-breath-hold MR cholangiography is not invasive and does not use ionizing radiation and potentially toxic contrast agents, it is recommended as the imaging technique of choice in children with choledochal cysts. CT cholangiography can be considered as an adjunct after surgery and in patients in whom MR cholangiography is unsatisfactory.     

Fine needle transhepatic cholangiography: a new approach to obstructive jaundice.

Transhepatic cholangiography performed with a newly introduced fine caliber (0.7 mm OD) "Chiba" needle produces a significantly higher success rate of biliary duct opacification with fewer complications than conventional needle or flexible cannula techniques. Distinct advantages over endoscopic retrograde cholangiography are also apparent, including more frequent bile duct opacification, ease of performance, and lower overall cost. In a group of 50 consecutive patients examined with the fine needle puncture technique, duct opacification was achieved in 92%, including 33 of 33 (100%) of patients with surgically obstructed ducts and 14 of 17 (82%) with normal caliber or narrowed ducts. Fine needle hepatic puncture is recommended as the preferred approach for direct biliary duct opacification in jaundiced patients.     

Early biliary complications of laparoscopic cholecystectomy: evaluation on T2-weighted MR cholangiography in conjunction with mangafodipir trisodium-enhanced 3D T1-weighted MR cholangiography

OBJECTIVE: Our aim was to assess preliminary experience with combined conventional T2-weighted and mangafodipir trisodium (MnDPDP)-enhanced T1-weighted MR cholangiography in evaluating early biliary complications of laparoscopic cholecystectomy. SUBJECTS AND METHODS: Conventional heavily T2-weighted MR cholangiography with MnDPDP-enhanced T1-weighted MR cholangiography and ERCP were performed in seven patients with high clinical suspicion of biliary complications after laparoscopic cholecystectomy. The final diagnoses of complications were classified according to the presence and degree of bile duct injury, bile leakage, and retained stones. RESULTS: The diagnoses on MR cholangiography were as follows: complete transection and occlusion of the common bile duct with bile leakage (n = 3), partial strictures of the common bile duct with bile leakage (n = 1), cystic duct leakage (n = 1), partial ligation of an aberrant right hepatic duct (n = 1), and hemorrhage without biliary complication (n = 1). The final diagnoses at surgery (n = 2) and ERCP (n = 5) were as follows: complete transection and occlusion of the common bile duct with bile leakage (n = 2), partial strictures of the common bile duct with bile leakage (n = 2), cystic duct leakage (n = 1), partial ligation of an aberrant right hepatic duct (n = 1), and hemorrhage without biliary complication (n = 1). MR cholangiography accurately yielded the same findings as the final diagnoses, except in one case with partial stricture of the bile duct with bile leakage (overdiagnosed as complete occlusion on MR cholangiography). CONCLUSION: Combined conventional T2-weighted and MnDPDP-enhanced T1-weighted MR cholangiography may eliminate the use of other studies for the imaging of biliary complications after cholecystectomy if this preliminary data can be verified in a larger study.     

Fine needle cholangiography in postcholecystectomy patients.

Thirteen cholecystectomized patients with postcholecystectomy symptoms are described. The patients were investigated with a combination of intravenous cholangiography and fine needle cholangiography. Fine needle cholangiography was found useful in patients with nonvisualized or questionably abnormal bile ducts on intravenous cholangiography. In one patient the intravenous cholangiogram was normal, but percutaneous cholangiography demonstrated calculi.     

Combined fine needle percutaneous transhepatic cholangiography and hypotonic duodenography in obstructive jaundice.

The information obtained at percutaneous transhepatic cholangiography in patients with obstructive jaundice is not always conclusive about the nature of the obstructing lesion. Hypotonic duodenography performed immediately after transhepatic cholangiography may assist in such cases by demonstrating the presence or absence of duodenal involvement. This ensures that the appropriate surgical procedure can be planned before operation. Our experience using the combined techniques in nine patients is reported.     

Radiological investigation in laparoscopic compared with conventional cholecystectomy--an early assessment.

The implications of laparoscopic cholecystectomy (LC) for radiology were assessed by comparing imaging investigations in 48 LC and 48 conventional cholecystectomy (CC) patients. In addition, we attempted to identify findings on pre-operative ultrasound (US) which predicted operative difficulties at LC. There were no per-operative or T-tube cholangiograms in the LC patients, but otherwise the pattern of investigation was similar in both groups. Forty of the 48 CC patients underwent cholangiography (per-operative cholangiography in 36, endoscopic retrograde cholangiopancreatography (ERCP) in two, and both in two) demonstrating calculi in eight (16.7%) cases. Only four LC patients had cholangiography (ERCP in all cases) demonstrating common bile duct (CBD) calculi in one (2.1%) case. Ultrasound failed to identify the gall-bladder with certainty in three of the five failed LC cases. Neither gall-bladder wall thickness, contraction nor calculus size on pre-operative US served as predictors of other per-operative difficulties. Our results indicate that there may be some patients with retained CBD calculi in the LC group. The role of pre-operative US in predicting operative difficulties needs further assessment in a prospective study.     

Diuretic radionuclide urography

Diuretic radionuclide urography is a modification of conventional renography which utilizes the administration of intravenous furosemide to distinguish dilated, non-obstructed, hydronephrotic systems from those with significant mechanical obstruction. Diagnostic patterns are derived from computer generated time-activity histograms that depict the accumulation and washout of radiotracer before and after diuretic injection. In dilated but non-obstructed systems, diuresis produces a decline in activity. In obstructed systems, there is a failure of radiotracer washout in response to diuresis and no decline in activity is observed. The procedure is applicable to patients of all ages with suspected upper urinary tract obstruction. Clinical and experimental data support the accuracy and utility of this methodology and define its limitations and pitfalls.     

MR cholangiography of late biliary complications after liver transplantation.

OBJECTIVE: The aim of our study was to assess the role of MR cholangiography in the diagnosis of late biliary complications after liver transplantation. SUBJECTS AND METHODS: Twenty-three liver transplantation patients (18 men and five women; mean age, 46 years) underwent MR cholangiography using a nonbreath-hold, fat-suppressed three-dimensional turbo spin-echo sequence (TR/TE, 3000/700; echo train length, 128) optimized on a 0.5-T magnet. Inclusion criteria were liver function tests with abnormal results and hyperbilirubinemia with a clinical pattern not specific for biliary obstruction. All patients were referred by clinicians for contrast-enhanced cholangiography. Diagnostic confirmation was obtained with percutaneous transhepatic cholangiography (n = 4), endoscopic retrograde cholangiography (n = 8), T-tube cholangiography (n = 1), or clinical follow-up (n = 10). RESULTS: In 11 patients, no abnormalities of the biliary tract were revealed by MR cholangiography. In 11 patients, twelve strictures were diagnosed (nine anastomotic, two nonanastomotic-intrahepatic, and one nonanastomotic-extrahepatic, with association between anastomotic and nonanastomotic strictures in two cases). In one other patient, kinking of the common bile duct at the level of the anastomosis was observed. In all cases, MR cholangiography correctly showed the site of the stricture and the dilatation of bile ducts above, with excellent correlation with contrast-enhanced cholangiographic findings. Strictures were correctly graded in eight of 10 patients and were overestimated in two. Other findings included a 1-cm stone detected proximal to the obstructed common bile duct in one patient and multiple intrahepatic stones in another patient. CONCLUSION: MR cholangiography can show biliary obstruction and provide important information for planning therapeutic procedures.     

The role of endoscopic retrograde cholangiography in the diagnosis and management of patients with primary sclerosing cholangitis.

The clinical and radiological findings in four patients with primary sclerosing cholangitis one of whom had coexistent cholangiocarcinoma, are reported. The need for surgical exploration to make the diagnosis was averted by the use of endoscopic retrograde cholangiography in one patient who was managed initially with medical treatment alone. Endoscopic cholangiography may be used to monitor the progress of the sclerosing lesions; but failure to fill the intrahepatic ducts is associated with a poor prognosis due either to the severity of the sclerosing process or the presence of coexistent cholangiocarcinoma.     

Multislice CT cholangiography without biliary contrast agent: technique and initial clinical results in the assessment of patients with biliary obstruction

Our objective was to describe our technique for multislice CT cholangiography without cholangiographic contrast agent, and to present our preliminary clinical results. Thirty-seven patients with suspected biliary obstruction were studied. A multislice CT unit was used with the following technical parameters: 2.5-mm collimation; 7.5-mm/s table speed; pitch 6; 0.8-s rotation time; 300 mA; 120 kVp; 18- to 24-s scan time; scan volume ranging from the hepatic dome to below the pancreatic head; 70-s delay after injection of 150 ml of iodinated contrast agent at 4 ml/s. No biliary contrast material was given; oral iodinated contrast agent was administered to opacify bowel loops. Axial, multiplanar reformatted, and minimum intensity projection images were evaluated. The CT findings were compared with the gold standard techniques: endoscopic retrograde cholangiography (ERCP) in 30 patients, percutaneous transhepatic cholangiography in 5, and intraoperative cholangiography in 2. In 5 patients with ampullary lesions biopsy was made during ERCP, 9 underwent surgery, and 11 US-guided fine-needle aspiration. Bile ducts appeared hypodense within the surrounding enhanced structures. Regarding the site of obstruction, agreement between multislice CT and conventional cholangiography was observed in all cases. One patient presented negative findings on both CT and ERCP. In 31 of 36 (86%) patients, multislice CT cholangiography without cholangiographic contrast agent correctly assessed the cause of bile duct obstruction. Multislice CT cholangiography without cholangiographic contrast agent seems to be a promising diagnostic tool in the assessment of patients with bile duct obstruction. Electronic Publication     

Diagnosing bile duct stones: comparison of unenhanced helical CT, oral contrast-enhanced CT cholangiography, and MR cholangiography

OBJECTIVE. In this investigation we compared the diagnostic performance of unenhanced helical CT, oral contrast-enhanced CT cholangiography, and MR cholangiography for the diagnosis of choledocholithiasis. SUBJECTS AND METHODS. Fifty-one patients referred for endoscopic retrograde cholangiography of suspected biliary stones were studied with unenhanced helical CT, MR cholangiography, and helical CT performed after oral administration of a cholangiographic contrast agent (iopodic acid). The studies were randomized for interpretation. Two radiologists evaluated the images by consensus and determined the presence and location of stones. We used retrograde cholangiography findings as the standard of reference. Sensitivity and specificity (with 95% confidence intervals [CIs]) of the three examinations were calculated and compared using the exact form of the McNemar test. RESULTS. Bile duct stones were revealed with retrograde cholangiography in 26 patients (51%). Sensitivity was 65% (95% CI, 44.4-82%) for unenhanced helical CT, 92% (95% CI, 73-99%) for CT cholangiography, and 96% (95% CI, 78-99%) for MR cholangiography. Specificity was 84% (95% CI, 63-95%) for unenhanced helical CT, 92% (95% CI, 73-99%) for CT cholangiography, and 100% (95% CI, 83-100%) for MR cholangiography. The sensitivity of CT cholangiography and MR cholangiography was significantly higher than that of unenhanced helical CT (p<0.01). Differences in specificity were not significant. CONCLUSION. Our results indicate that oral contrast-enhanced CT cholangiography and MR cholangiography are significantly more sensitive than unenhanced helical CT for the detection of bile duct calculi.     

The role of model-based methods in the development of single scan techniques

Single scan techniques are highly desirable for clinical trials involving radiotracers because they increase logistical feasibility, improve patient compliance, and decrease the cost associated with the study. However, the information derived from single scans usually are biased by factors unrelated to the process of interest. Therefore, identification of these factors and evaluation of their impact on the proposed outcome measure is important. In this paper, the impact of confounding factors on single scan measurements is illustrated by discussing the effect of between-subject or between-condition differences in radiotracer plasma clearance on normalized activity ratios (specific to nonspecific ratios) in the tissue of interest. Computer simulation based on kinetic analyses are presented to demonstrate this effect. It is proposed that the presence of this and other confounding factors should not necessarily preclude clinical trials based on single scan techniques. First, knowledge of the distribution of plasma clearance values in a sample of the investigated population allows researchers to assign limits to this potential bias. This information can be integrated in the power analysis. Second, the impact of this problem will vary according to the characteristic of the radiotracer, and this information can be used in the development and selection of the radiotracer. Third, simple modification of the experimental design (such as administration of the radiotracer as a bolus, followed by constant infusion, rather than as a single bolus) might remove this potential confounding factor and allow appropriate quantification within the limits of a single scanning session. In conclusion, model-based kinetic characterization of radiotracer distribution and uptake is critical to the design and interpretation of clinical trials based on single scan techniques.