Comparison of the gamma-Pareto convolution with conventional methods of characterising metformin pharmacokinetics in dogs.

A model was developed for long term metformin tissue retention based upon temporally inclusive models of serum/plasma concentration ([Formula: see text]) having power function tails called the gamma-Pareto type I convolution (GPC) model and was contrasted with biexponential (E2) and noncompartmental (NC) metformin models. GPC models of [Formula: see text] have a peripheral venous first arrival of drug-times parameter, early [Formula: see text] peaks and very slow washouts of [Formula: see text]. The GPC, E2 and NC models were applied to a total of 148 serum samples drawn from 20 min to 72 h following bolus intravenous metformin in seven healthy mongrel dogs. The GPC model was used to calculate area under the curve (AUC), clearance ([Formula: see text]), and functions of time, f(t), for drug mass remaining (M), apparent volume of distribution ([Formula: see text]), as well as [Formula: see text] for [Formula: see text], [Formula: see text] and [Formula: see text]. The GPC models of [Formula: see text] yielded metformin [Formula: see text]-values that were 84.8% of total renal plasma flow (RPF) as estimated from meta-analysis. The GPC [Formula: see text]-values were significantly less than the corresponding NC and E2 [Formula: see text]-values of 104.7% and 123.7% of RPF, respectively. The GPC plasma/serum only model predicted 78.9% drug [Formula: see text] average urinary recovery at 72 h; similar to prior human urine drug [Formula: see text] collection results. The GPC model [Formula: see text] of [Formula: see text], [Formula: see text] and [Formula: see text], were asymptotically proportional to elapsed time, with a constant limiting [Formula: see text] ratio of M/C averaging 7.0 times, a result in keeping with prior simultaneous [Formula: see text] and urine [Formula: see text] collection studies and exhibiting a rate of apparent volume growth of [Formula: see text] that achieved limiting constant values. A simulated constant average drug mass multidosing protocol exhibited increased [Formula: see text] and [Formula: see text] with elapsing time, effects that have been observed experimentally during same-dose multidosing. The GPC heavy-tailed models explained multiple documented phenomena that were unexplained with lighter-tailed models.

Incidence and Economic Impact of Incidental Findings on 18F-FDG PET/CT Imaging.

PURPOSE: The study sought to determine the incidence of incidental findings on whole-body positron emission tomography with computed tomography (PET/CT) imaging and the average costs of investigations to follow-up or further characterize incidental findings. METHODS: Imaging reports of 215 patients who underwent whole-body PET/CT imaging were retrospectively reviewed. Our provincial picture archiving and communication system was queried and patient charts were reviewed to identify all investigations performed to follow-up incidental findings within 1 year of the initial PET/CT study. Costs of follow-up imaging studies (professional and technical components) and other diagnostic tests and procedures were determined in Canadian dollars (CAD) and U.S. dollars (USD) using the 2015 Ontario Health Insurance Plan Schedule of Benefits and Fees and 2016 U.S. Medicare Physician Fee Schedule, respectively. RESULTS: At least 1 incidental finding was reported in 161 reports (74.9%). The mean number of incidental findings ranged from 0.64 in patients <45 years of age to 2.2 in patients 75 years of age and older. Seventy-five recommendations for additional investigations were made for 64 (30%) patients undergoing PET/CT imaging, and 14 of those were carried out specifically to follow-up incidental findings. Averaged across all 215 patients, the total cost of investigations recommended to follow-up incidental findings was CAD$105.51 (USD$127.56) per PET/CT study if all recommendations were acted on, and CAD$22.77 (USD$29.14) based on investigations actually performed. CONCLUSIONS: As the incidence of incidental findings increases with age and a larger proportion of elderly patients is expected as population demographics change, it will be increasingly important to consider incidental findings on PET/CT imaging with standardized approaches to follow-up.

Imaging of late complications of cancer therapy in children.

Long-term survival after childhood cancer has improved dramatically over recent decades but survivors face lifelong risks of adverse health effects. Many of these chronic conditions are a direct result of previous therapeutic exposures. Compared to their siblings, survivors face a greater than 8-fold increase in relative risk of severe or life-threatening medical conditions; the most significant of these include second malignancies and cardiovascular and pulmonary diseases. Imaging can play a key role in identifying and characterizing such complications, which can be reasonably predicted with knowledge of the child's treatment. This article highlights the varied radiologic presentations and features seen in late cancer-therapy-related conditions.

Initial Experience Using a Telerobotic Ultrasound System for Adult Abdominal Sonography.

PURPOSE: The study sought to assess the feasibility of performing adult abdominal examinations using a telerobotic ultrasound system in which radiologists or sonographers can control fine movements of a transducer and all ultrasound settings from a remote location. METHODS: Eighteen patients prospectively underwent a conventional sonography examination (using EPIQ 5 [Philips] or LOGIQ E9 [GE Healthcare]) followed by a telerobotic sonography examination (using the MELODY System [AdEchoTech] and SonixTablet [BK Ultrasound]) according to a standardized abdominal imaging protocol. For telerobotic examinations, patients were scanned remotely by a sonographer 2.75 km away. Conventional examinations were read independently from telerobotic examinations. Image quality and acceptability to patients and sonographers was assessed. RESULTS: Ninety-two percent of organs visualized on conventional examinations were sufficiently visualized on telerobotic examinations. Five pathological findings were identified on both telerobotic and conventional examinations, 3 findings were identified using only conventional sonography, and 2 findings were identified using only telerobotic sonography. A paired sample t test showed no significant difference between the 2 modalities in measurements of the liver, spleen, and diameter of the proximal aorta; however, telerobotic assessments overestimated distal aorta and common bile duct diameters and underestimated kidney lengths (P values < .05). All patients responded that they would be willing to have another telerobotic examination. CONCLUSIONS: A telerobotic ultrasound system is feasible for performing abdominal ultrasound examinations at a distant location with minimal training and setup requirements and a moderate learning curve. Telerobotic sonography (robotic telesonography) may open up the possibility of remote ultrasound clinics for communities that lack skilled sonographers and radiologists, thereby improving access to care.

Liver MR Imaging in Children: Current Concepts and Technique.

Magnetic resonance (MR) imaging is increasingly being used for comprehensive evaluation of liver diseases in children because of the lack of radiation and better lesion detection and characterization. Liver examination involves routine sequences such as T2-weighted, balanced steady-state free precession, and in-phase and out-of-phase sequences. Dynamic imaging is an essential component of liver examination to characterize focal lesions and involves capturing snapshots of the passage of contrast material in the arterial, portal venous, equilibrium, and sometimes hepatobiliary phases, generally by using T1-weighted three-dimensional gradient-echo sequences. Optimal arterial phase imaging is important for detection and characterization of hypervascular lesions. In the equilibrium phase, the concentration of contrast material is similar in the microvasculature and the extracellular interstitial space. Some superficial, spreading, inflammatory lesions are better seen on equilibrium phase images. Meticulous attention to intravenous access and use of an appropriate timing method are critical for successful dynamic imaging. Commonly used contrast media for liver imaging include gadolinium-based extracellular contrast agents and hepatobiliary contrast agents. A portion of hepatobiliary contrast agents such as gadoxetate and gadobenate is taken up by hepatocytes and excreted through bile. Hepatobiliary phase images acquired after hepatobiliary contrast agent administration are increasingly used to characterize liver lesions in children, such as focal nodular hyperplasia. Interpretation of liver MR images involves synthesis of information acquired from evaluation of background hepatic parenchyma, detection of lesions, and evaluation of signal intensity characteristics on images obtained with various sequences to arrive at a diagnosis or reasonable differential diagnoses. Understanding the appropriate technique, sequences, and contrast media when performing pediatric liver MR imaging is important for high diagnostic yield. (©)RSNA, 2016.

Imaging of acute and subacute toxicities of cancer therapy in children.

Effective cancer therapies have resulted in significant improvement in survival. However, treatment-related acute and subacute complications are a cause of significant morbidity and mortality. Effects of cancer therapy in children can be seen early in the survival period or later in life in almost all organ systems of the body. Many of these conditions are evaluated by imaging and some are diagnosed based on characteristic imaging features. This article aims to discuss acute and subacute toxicities of cancer therapy in children involving multiple organ systems, pulmonary, gastrointestinal, hepatobiliary, genitourinary and musculoskeletal systems with emphasis on those in which imaging plays a role in diagnosis or management. We also discuss the role of imaging and choice of imaging modalities in these conditions.

Pediatric Body MR Angiography: Principles, Techniques, and Current Status in Body Imaging.

OBJECTIVE: The purpose of this article is to describe the principles and various techniques of MR angiography (MRA) that can be applied to pediatric body imaging and the current noncardiac, nonneurologic applications of MRA of children. CONCLUSION: The choice between CT angiography and MRA for body imaging should depend on the clinical query, ROI, and vessel size. MRA is useful for assessment of stenosis of the main renal artery, portal hypertension, tumor vascularity, vascular malformations, generalized vasculopathy in vasculitis and syndromes, and thoracic outlet syndrome.

Metal Artifact Reduction: Added Value of Rapid-Kilovoltage-Switching Dual-Energy CT in Relation to Single-Energy CT in a Piglet Animal Model.

OBJECTIVE: The purpose of this article is to evaluate virtual monochromatic spectral imaging and metal artifact reduction software for reducing metal artifact and to compare it with conventional single-energy CT (SECT) in an animal model. MATERIALS AND METHODS: Postmortem juvenile (n = 5) and adult (n = 1) swine specimens were scanned with SECT followed by a dual-energy CT (DECT) pediatric protocol after the insertion of two rods into their paraspinal thoracolumbar regions. Virtual monochromatic spectral images were extrapolated from DECT images at five monoenergetic levels (64, 69, 75, 88, and 105 keV) with and without the use of metal artifact reduction software. Images were evaluated by a 5-point scoring system for the extent of metallic artifacts and image interpretability in soft-tissue and bone windows. The density in the most pronounced artifact was measured. CT dose index was recorded. RESULTS: In studies without metal artifact reduction software, higher energy reconstructions resulted in fewer artifacts and better image interpretability in both soft-tissue and bone windows (p < 0.0001). Artifact density decreased from -792 HU at 64 keV to -128 HU at 105 keV without the use of metal artifact reduction software. No difference was noted in attributes' scores or in artifact density in studies using metal artifact reduction software (p > 0.05). DECT studies showed lower scores compared with SECT with regard to all attributes. A new faint perimetallic hypodense halo was seen in all studies with metal artifact reduction software. The CT dose index of DECT was 1.18-3.56 times higher than that of SECT techniques. CONCLUSION: DECT at all energy levels with metal artifact reduction software and higher energy extrapolations without metal artifact reduction software reduced metallic artifact and enhanced image interpretability compared with SECT. Radiation dose with DECT could be significantly higher than SECT.

Diffusion-weighted imaging in pediatric body MR imaging: principles, technique, and emerging applications.

Diffusion-weighted (DW) imaging is an emerging technique in body imaging that provides indirect information about the microenvironment of tissues and lesions and helps detect, characterize, and follow up abnormalities. Two main challenges in the application of DW imaging to body imaging are the decreased signal-to-noise ratio of body tissues compared with neuronal tissues due to their shorter T2 relaxation time, and image degradation related to physiologic motion (eg, respiratory motion). Use of smaller b values and newer motion compensation techniques allow the evaluation of anatomic structures with DW imaging. DW imaging can be performed as a breath-hold sequence or a free-breathing sequence with or without respiratory triggering. Depending on the mobility of water molecules in their microenvironment, different normal tissues have different signals at DW imaging. Some normal tissues (eg, lymph nodes, spleen, ovarian and testicular parenchyma) are diffusion restricted, whereas others (eg, gallbladder, corpora cavernosa, endometrium, cartilage) show T2 shine-through. Epiphyses that contain fatty marrow and bone cortex appear dark on both DW images and apparent diffusion coefficient maps. Current and emerging applications of DW imaging in pediatric body imaging include tumor detection and characterization, assessment of therapy response and monitoring of tumors, noninvasive detection and grading of liver fibrosis and cirrhosis, detection of abscesses, and evaluation of inflammatory bowel disease.

Gadobenate-dimeglumine-enhanced magnetic resonance imaging for hepatic lesions in children.

BACKGROUND: Magnetic resonance imaging enhanced by hepatocyte-specific contrast media has been found useful to characterize liver lesions in adults and children. OBJECTIVE: To present our experience with gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI for evaluation of focal liver lesions in children. MATERIALS AND METHODS: We retrospectively reviewed gadobenate-dimeglumine-enhanced MR images obtained for evaluation of suspected hepatic lesions in 30 children. Signal characteristics on various sequences including 45- to 60-min hepatobiliary phase images were noted by two radiologists. Chart review identified relevant clinical details including history of cancer treatment, available pathology and stability of lesion size on follow-up imaging. RESULTS: Of the 30 children who had gadobenate-enhanced MRI, 26 showed focal lesions. Diagnoses in 26 children were focal nodular hyperplasia (FNH) in 15, hemangiomas in 3, regenerating nodules in 3, focal fatty infiltration in 2, indeterminate lesions in 3, and one patient each with adenomas, hepatoblastoma and metastasis. Two patients had multiple diagnoses. All FNH lesions (39), all regenerative nodules (19) and an indeterminate lesion were iso- or hyperintense on hepatobiliary-phase images while all other lesions (28) were hypointense to hepatic parenchyma. The average follow-up period was 21.7 months. CONCLUSION: Our experience with gadobenate-enhanced MRI indicates potential utility of gadobenate in the evaluation of pediatric hepatic lesions in differentiating FNH and regenerating nodules from other lesions.

Deep learning-based age estimation from chest CT scans.

PURPOSE: Medical imaging can be used to estimate a patient's biological age, which may provide complementary information to clinicians compared to chronological age. In this study, we aimed to develop a method to estimate a patient's age based on their chest CT scan. Additionally, we investigated whether chest CT estimated age is a more accurate predictor of lung cancer risk compared to chronological age. METHODS: To develop our age prediction model, we utilized composite CT images and Inception-ResNet-v2. The model was trained, validated, and tested on 13,824 chest CT scans from the National Lung Screening Trial, with 91% for training, 5% for validation, and 4% for testing. Additionally, we independently tested the model on 1849 CT scans collected locally. To assess chest CT estimated age as a risk factor for lung cancer, we computed the relative lung cancer risk between two groups. Group 1 consisted of individuals assigned a CT age older than their chronological age, while Group 2 comprised those assigned a CT age younger than their chronological age. RESULTS: Our analysis revealed a mean absolute error of 1.84 years and a Pearson's correlation coefficient of 0.97 for our local data when comparing chronological age with the estimated CT age. The model showed the most activation in the area associated with the lungs during age estimation. The relative risk for lung cancer was 1.82 (95% confidence interval, 1.65-2.02) for individuals assigned a CT age older than their chronological age compared to those assigned a CT age younger than their chronological age. CONCLUSION: Findings suggest that chest CT age captures some aspects of biological aging and may be a more accurate predictor of lung cancer risk than chronological age. Future studies with larger and more diverse patients are required for the generalization of the interpretations.

Whole-body MR imaging for staging of malignant tumors in pediatric patients: results of the American College of Radiology Imaging Network 6660 Trial.

PURPOSE: To compare whole-body magnetic resonance (MR) imaging with conventional imaging for detection of distant metastases in pediatric patients with common malignant tumors. MATERIALS AND METHODS: This institutional review board-approved, HIPAA-compliant, multicenter prospective cohort study included 188 patients (109 male, 79 female; mean age, 10.2 years; range, < 1 to 21 years) with newly diagnosed lymphoma, neuroblastoma, or soft-tissue sarcoma. Informed consent was obtained and all patients underwent noncontrast material-enhanced whole-body MR imaging and standard-practice conventional imaging. All images were reviewed centrally by 10 pairs of readers. An independent panel verified the presence or absence of distant metastases. Detection of metastasis with whole-body MR and conventional imaging was quantified by using the area under the receiver operating characteristic curve (AUC). The effects of tumor subtype, patient age, and distant skeletal and pulmonary disease on diagnostic accuracy were also analyzed. RESULTS: Of the 134 eligible patients, 66 (33 positive and 33 negative for metastasis) were selected for image review and analysis. Whole-body MR imaging did not meet the noninferiority criterion for accuracy when compared with conventional imaging for detection of metastasis (difference between average AUCs was -0.03 [95% confidence interval: -0.10, 0.04]); however, the average AUC for solid tumors was significantly higher than that for lymphomas (P = .006). More skeletal metastases were detected by using whole-body MR imaging than by using conventional imaging (P = .03), but fewer lung metastases were detected (P < .001). Patient age did not affect accuracy. CONCLUSION: The noninferior accuracy for diagnosis of distant metastasis in patients with common pediatric tumors was not established for the use of whole-body MR imaging compared with conventional methods. However, improved accuracy was seen with whole-body MR imaging in patients with nonlymphomatous tumors.

Abdominal MR imaging in children: motion compensation, sequence optimization, and protocol organization.

Familiarity with basic sequence properties and their trade-offs is necessary for radiologists performing abdominal magnetic resonance (MR) imaging. Acquiring diagnostic-quality MR images in the pediatric abdomen is challenging due to motion, inability to breath hold, varying patient size, and artifacts. Motion-compensation techniques (eg, respiratory gating, signal averaging, suppression of signal from moving tissue, swapping phase- and frequency-encoding directions, use of faster sequences with breath holding, parallel imaging, and radial k-space filling) can improve image quality. Each of these techniques is more suitable for use with certain sequences and acquisition planes and in specific situations and age groups. Different T1- and T2-weighted sequences work better in different age groups and with differing acquisition planes and have specific advantages and disadvantages. Dynamic imaging should be performed differently in younger children than in older children. In younger children, the sequence and the timing of dynamic phases need to be adjusted. Different sequences work better in smaller children and in older children because of differing breath-holding ability, breathing patterns, field of view, and use of sedation. Hence, specific protocols should be maintained for younger children and older children. Combining longer-higher-resolution sequences and faster-lower-resolution sequences helps acquire diagnostic-quality images in a reasonable time.

Comparison of respiratory-triggered 3-D fast spin-echo and single-shot fast spin-echo radial slab MR cholangiopancreatography images in children.

BACKGROUND: The two most commonly performed magnetic resonance cholangiopancreatography (MRCP) sequences, 3-D fast spin-echo (3-D FSE) and single-shot fast spin-echo radial slabs (radial slabs), have not been compared in children. OBJECTIVE: The purpose of this study was to compare 3-D FSE and radial slabs MRCP sequences on a 3-T scanner to determine their ability to show various segments of pancreaticobiliary tree and presence of artifacts in children. MATERIALS AND METHODS: We reviewed 79 consecutive MRCPs performed in 74 children on a 3-T scanner. We noted visibility of major ducts on 3-D FSE and radial slabs. We noted the order of branching of ducts in the right and left hepatic ducts and the degree of visibility of the pancreatic duct. Statistical analysis was performed using McNemar and signed rank tests. RESULTS: There was no significant difference in the visibility of major bile ducts and the order of branching in the right hepatic lobe between sequences. A higher order of branching in the left lobe was seen on radial slabs than 3-D FSE (mean order of branching 2.82 versus 2.27; P-value = 0.0002). The visibility of pancreatic duct was better on radial slabs as compared to 3-D FSE (mean value of 1.53 vs. 0.90; P-value < 0.0001). 3-D FSE sequence was artifact-free in 25/79 (31.6%) MRCP exams as compared to radial slabs, which were artifact-free in 18/79 (22.8%) MRCP exams (P-value = 0.0001). CONCLUSION: There is no significant difference in the visibility of major bile ducts between 3-D FSE and radial slab MRCP sequences at 3-T in children. However, radial slab MRCP shows a higher order of branching in the left hepatic lobe and superior visibility of the pancreatic duct than 3-D FSE.

Diagnosis of postoperative bile leak and accurate localization of the site of leak by gadobenate dimeglumine-enhanced MR cholangiography in a child.

Postoperative bile leaks are difficult to diagnose because signs and symptoms are nonspecific, and definitive diagnosis requires a drainage catheter to be placed that drains frank bile or fluid that turns out bile on laboratory analysis. Hepatobiliary scintigraphy, endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) have been traditionally used to diagnose bile leak. Scintigraphy has poor spatial resolution and cannot localize the site of leak, ERCP may not be possible with altered postoperative anatomy and PTC is invasive and difficult to perform in the absence of dilated ducts. Recently, contrast-enhanced MR cholangiography using hepatobiliary-specific contrast media has been shown to be a noninvasive, safe way to diagnose and localize the site of bile leak in adults. We report a case of postoperative bile leak after choledochal cyst resection in a child in whom diagnosis was confirmed and the site of leak was accurately localized using gadobenate-enhanced MR cholangiography. This case demonstrates the potential of hepatobiliary-specific contrast media to diagnose postoperative bile leak and accurately localize the site of the leak in children noninvasively.

Applications of deep learning to reduce the need for iodinated contrast media for CT imaging: a systematic review.

PURPOSE: The usage of iodinated contrast media (ICM) can improve the sensitivity and specificity of computed tomography (CT) for many clinical indications. However, the adverse effects of ICM administration can include renal injury, life-threatening allergic-like reactions, and environmental contamination. Deep learning (DL) models can generate full-dose ICM CT images from non-contrast or low-dose ICM administration or generate non-contrast CT from full-dose ICM CT. Eliminating the need for both contrast-enhanced and non-enhanced imaging or reducing the amount of required contrast while maintaining diagnostic capability may reduce overall patient risk, improve efficiency and minimize costs. We reviewed the current capabilities of DL to reduce the need for contrast administration in CT. METHODS: We conducted a systematic review of articles utilizing DL to reduce the amount of ICM required in CT, searching MEDLINE, Embase, Compendex, Inspec, and Scopus to identify papers published from 2016 to 2022. We classified the articles based on the DL model and ICM reduction. RESULTS: Eighteen papers met the inclusion criteria for analysis. Of these, ten generated synthetic full-dose (100%) ICM from real non-contrast CT, while four augmented low-dose to full-dose ICM CT. Three used DL to create synthetic non-contrast CT from real 100% ICM CT, while one paper used DL to translate the 100% ICM to non-contrast CT and vice versa. DL models commonly used generative adversarial networks trained and tested by paired contrast-enhanced and non-contrast or low ICM CTs. Image quality metrics such as peak signal-to-noise ratio and structural similarity index were frequently used for comparing synthetic versus real CT image quality. CONCLUSION: DL-generated contrast-enhanced or non-contrast CT may assist in diagnosis and radiation therapy planning; however, further work to optimize protocols to reduce or eliminate ICM for specific pathology is still needed along with a dedicated assessment of the clinical utility of these synthetic images.

Utility of CT in the diagnosis and management of small-bowel obstruction in children.

BACKGROUND: CT is often used in the diagnosis and management of small-bowel obstruction in children. OBJECTIVE: To determine sensitivity of CT in delineating presence, site and cause of small-bowel obstruction in children. MATERIALS AND METHODS: We retrospectively reviewed the CT scans of 47 children with surgically proven small-bowel obstruction. We noted any findings of obstruction and the site and cause of obstruction. Presence, absence or equivocal findings of bowel obstruction on abdominal radiographs performed prior to CT were also noted. We reviewed patient charts for clinical details and surgical findings, including bowel resection. Statistical analysis was performed using Fisher exact test to determine which CT findings might predict bowel resection. RESULTS: CT correctly diagnosed small-bowel obstruction in 43/47 (91.5%) cases. CT correctly indicated site of obstruction in 37/47 (78.7%) cases and cause of obstruction in 32/47 (68.1%) cases. Small-bowel feces sign was significantly associated with bowel resection at surgery (P = 0.0091). No other CT finding was predictive of bowel resection. Out of 41 children who had abdominal radiographs before CT, 29 (70.7%) showed unequivocal obstruction, six (14.6%) showed equivocal findings and six (14.6%) were unremarkable. CONCLUSION: CT is highly sensitive in diagnosing small-bowel obstruction in children and is helpful in determining the presence of small-bowel obstruction in many clinically suspected cases with equivocal or normal plain radiographs. CT also helps to determine the site and cause of the obstruction with good sensitivity.

Validation of Tikhonov adaptively regularized gamma variate fitting with 24-h plasma clearance in cirrhotic patients with ascites.

PURPOSE: The aim was to compare late-time extrapolation of plasma clearance (CL) from Tikhonov adaptively regularized gamma variate fitting (Tk-GV) and from mono-exponential (E1) fitting. METHODS: Ten (51)Cr-ethylenediaminetetraacetic acid bolus IV studies in adults--8 with ascites--assessed for liver transplantation, with 12-16 plasma samples drawn from 5-min to 24-h, were fit with Tk-GV and E1 models and CL results were compared using Passing-Bablok fitting. RESULTS: The 24-h CL(Tk-GV) values ranged from 11.4 to 79.7 ml/min. Linear regression of 4- versus 24-h CL(Tk-GV) yielded no significant departure from a slope of 1, whereas the 4- versus 24-h CL(E1) slope, 1.56, was significantly increased. For CL(Tk-GV-24-h) versus CL(E1-24-h), there was a biased slope and intercept (0.85, 5.97 ml/min). Moreover, the quality of fitting of 24-h data was significantly better for Tk-GV than for E1, as follows. For 10 logarithm of concentration curves, higher r values were obtained for each Tk-GV fit (median 0.998) than for its corresponding E1 fit (median 0.965), with p < 0.0001 (paired t-test of z-statistics from Fisher r-z transformations). The E1 fit quality degraded with increasing V/W [volume of distribution (l) per kg body weight, p = 0.003]. However, Tk-GV fit quality versus V/W was uncorrelated (p = 0.8). CONCLUSION: CL(E1) values were dependent on sample time and the quality of fit was poor and degraded with increasing ascites, consistent with current opinion that CL(E1) is contraindicated in ascitic patients. CL(Tk-GV) was relatively more accurate and the good quality of fit was unaffected by ascites. CL(Tk-GV) was the preferred method for the accurate calculation of CL and was useful despite liver failure and ascites.