Effect of stifle angle on the magnitude of the tibial plateau angle measurement in dogs with intact and transected cranial cruciate ligament. A cadaveric study.

OBJECTIVE: To determine the effect of stifle angle on the magnitude of the radiographic tibial plateau angle (TPA) in normal and cranial cruciate ligament (CCL) -deficient stifles. METHODS: Three pairs of canine cadaver hindlimbs from three skeletally mature dogs were positioned in a custom-made positioning device. A lateral radiograph of each specimen was obtained before and after transection of the CCL at four stifle angles (90°, 110°, 135° and 140-150° [i.e. maximum extension]), based on goniometric measurements. Four observers determined the radiographic TPA twice for each radiograph with a minimum of two days between each measurement. The radiographic TPA measurements in all specimens at different stifle angles with intact CCL and transected CCL were compared with mixed-model ANOVA. The effect of stifle angle, CCL transection, and interaction between the two on observer TPA measurement variability was also determined using the coefficient of variation. RESULTS: Tibial plateau angle was not statistically different in the stifle angles for either the intact or transected CCL. There was also no statistical difference for TPA between intact and transected CCL groups at each of the stifle angles. Stifle angle, CCL transection and interaction between the two did not have any significant effect for intra-observer and inter-observer variation. CLINICAL SIGNIFICANCE: The angle of the stifle during radiography does not influence the magnitude of the TPA measurement as determined on true lateral radiographs of the stifle and tibia in cadaveric canine limbs.

Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient.

Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.

Quantitative analysis of the effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetyltriglycine in dogs.

Effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetylytriglycine (99mTc-MAG3) in dogs was investigated before (control), and after 15 min and 24 h of i.v. injection of probenecid (20 mg/kg). Plasma concentration-time profiles of 99mTc-MAG3 were described with a two-compartment open model. Plasma 99mTc-MAG3 clearances (Clp, ml/min/kg) were 7.9 +/- 0.5, 3.3 +/- 0.5 and 4.8 +/- 1.3 in control, 15 min and 24 h after probenecid administration respectively. Similarly, the biological half-lives at elimination phase (t(1/2), h) were 0.61 +/- 0.09, 0.79 +/- 0.11 and 0.74 +/- 0.12, and volumes of distribution at steady state (Vdss, L/kg) were 0.29 +/- 0.04, 0.20 +/- 0.05 and 0.25 +/- 0.06 respectively. The prolonged biological half-life and decreased Vdss decreased Clp significantly. Clp was a function of plasma probenecid concentration based on Michaelis-Menten kinetics. The maximum Clp inhibition (Imax) by probenecid and the plasma probenecid concentration that induced 50% of Imax (I50) were estimated to be 72 +/- 12% and 13 +/- 8 microg/ml respectively. This means that the rest (about 28%) of the Clp is not blocked by probenecid alone, suggesting the possibility of another route(s) of elimination or renal transporters which are independent from probenecid. Moreover, inter-species correlation between Clp of 99mTc-MAG3 and body weight are discussed.

The effect of methimazole on thyroid uptake of pertechnetate and radioiodine in normal cats.

Many hyperthyroid cats referred for thyroid imaging and 131I therapy are concurrently or recently receiving antithyroid medications. The effect of the antithyroid drug, methimazole, on thyroid uptake of 99mTcO4 and 123I was evaluated in 8 normal cats. Quantitative analysis was used to determine the normal percent dose uptake of 99mTcO4 and 123I, the change in thyroid:salivary ratios (T:S) of 99-TcO4 over time, and the duration of the methimazole effect on thyroid uptake of 123I. Methimazole was administered to 5 cats for 3 weeks in which a hypothyroid state was obtained; 3 cats served as non-treatment controls. 99mTcO4 and 8 and 24 hour 123I imaging was repeated after 3 weeks of methimazole therapy (time of maximum T4 suppression). Methimazole was then discontinued and 123I images and serum T4 concentrations were repeated at 1, 4, 9, 15, and 24 days post withdrawal. The percent dose uptake of 99mTcO4 increased throughout the acquisition period with maximum uptake occurring 4 hour post injection. The baseline 20 min. T:S ratio for controls and treatment cats were 0.79 +/- 0.08 and 0.81 +/- 0.05 respectively; with a peak value of 1.29 +/- 0.23 and 1.31 +/- 0.18 at 4 hours. The baseline T:S ratios were not significantly different from 20 minutes to 2 hours, however they were significantly elevated at 4 hours post injection. Baseline, 8 and 24 hour percent dose uptake of 123I were 2.1 +/- 0.42% and 7.04 +/- 1.24%, respectively. There was a significant increase in the T:S ratio in the treatment group at all time points. The 8 hour percent dose uptake of 123I at 1, 4, and 9 days post methimazole withdrawal were significantly increased and peaked at 4 days. The 24 hour uptake was significantly increased at 4 and 9 days, with peak uptake at 9 days post-methimazole withdrawal. The 123I percent dose uptake decreased to baseline values by day 15 post withdrawal. Radioiodine uptake is not inhibited by methimazole treatment in normal cats, and is significantly enhanced after recent withdrawal. This finding is supportive of a "short term rebund effect" with maximal enhanced uptake between 4 and 9 days after discontinuing antithyroid drugs. The increased uptake of 99mTcO4 may also affect the interpretation of 99mTcO4 thyroid scintigraphy for 2-3 weeks.

Evaluation of heart time-activity curves as a predictor of hepatic extraction of 99mTc-mebrofenin in dogs.

In this study, heart time-activity curve, created following intravenous injection of 99mTc-mebrofenin were used to quantify hepatic function in normal dogs and dogs with induced hepatic parenchymal cell damage. The results were compared to a direct measurement of hepatic extraction following mesenteric venous injection of 99mTc-mebrofenin. The heart time-activity curves were normalized and the area under the curve from 0-30 minutes and 0-60 minutes were determined. In addition, the half-time clearance rate of the heart time-activity curve was analyzed using a two-compartment model. Linear regression analysis was used to describe the relationship between the area under the normalized heart time-activity curve and hepatic extraction. There was good correlation between the area under the normalized heart time-activity curve and hepatic extraction. The best correlation was obtained from the 0-30 minute data (r2 = 0.92). A formula for calculating hepatic extraction was derived using linear regression analysis: Hepatic extraction = 1.092 - (0.0000308 x AUC0-30 minutes). There was good correlation between the half-time clearance rates from the heart time-activity curve and hepatic extraction. The best correlation was between the fast phase half-time clearance and hepatic extraction (r2 = 0.88). The area under a normalized heart time-activity curve can be used as a simple alternative to deconvolutional analysis for the determination of hepatic extraction as a measure of hepatic parenchymal cell function in the dog.

Cross-sectional imaging techniques in veterinary ophthalmology.

Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are useful, complementary cross-sectional imaging modalities of the eye and orbit. High-resolution US provides excellent morphological information of ocular structures but offers limited information on the periocular tissues. CT and MRI provide valuable morphologic and topographic images of both ocular and periocular structures, thereby giving a more complete picture of the pathological process. US can be performed on awake patients, whereas CT and MRI require general anesthesia. In addition, US equipment is readily available and less costly than CT or MRI units. Fine-needle aspirations and biopsies under US or CT guidance can also be performed. This article reviews the technique and normal findings of ocular and orbital structures as displayed in each of these imaging modalities. Representative clinical cases are presented to illustrate the interpretation principles as well as to provide an illustrative reference for common ocular and orbital changes.

The use of gated radionuclide ventriculography as a noninvasive method of evaluating right ventricular function in dogs with experimentally induced congestive heart failure.

Gated radionuclide ventriculography was evaluated as a noninvasive method of quantifying right ventricular function in dogs with experimentally induced congestive heart failure. Gated radionuclide ventriculography measurements of right ventricular function (right ventricular ejection fraction, right ventricular average emptying rate, and right ventricular average filling rate) were related to standard hemodynamic and echocardiographic measurements. Congestive heart failure was induced by rapid ventricular pacing in eight normal dogs. Hemodynamic, echocardiographic, and gated radionuclide ventriculography measurements were obtained before and after development of biventricular failure. Congestive heart failure resulted in significant changes in all hemodynamic, echocardiographic, and gated radionuclide ventriculography measurements with the exception of systemic arterial pressure. Right ventricular ejection fraction was inversely related to pulmonary artery systolic, diastolic, and mean pressure, and right ventricular average emptying rate was inversely related to the pulmonary artery systolic, diastolic, and mean pressure. Right ventricular ejection fraction was inversely related to left ventricular filling pressure, (pulmonary capillary wedge pressure). Neither the echocardiographic measurements of right ventricular size (right ventricular internal diastolic dimension) nor the right ventricular end-diastolic pressure were related to right ventricular ejection fraction and right ventricular average emptying rate. However, echocardiographic measurements of right ventricular dimension were related to right ventricular filling pressure. The gated radionuclide ventriculography indexes of right ventricular function, right ventricular ejection fraction and right ventricular average emptying rate, are affected by afterload but unaffected by preload, whereas the echocardiographic measurement of right ventricular dimension is related to preload. Gated radionuclide ventriculography provides right ventricular data which is unique from that obtained by standard echocardiographic imaging. Also, gated radionuclide ventriculography has potential value as a noninvasive means of estimating a change in pulmonary artery pressure.

Double-phase parathyroid scintigraphy in dogs using technetium-99M-sestamibi.

The purpose of this study was to evaluate the utility of double-phase parathyroid scintigraphy using 99mTc-sestamibi for detecting and localizing hyperfunctioning parathyroid glands in hypercalcemic dogs. Fifteen hypercalcemic dogs that underwent parathyroid scintigraphy were included in this study: 3 dogs with hypercalcemia of malignancy, and 12 dogs with hyperfunctioning parathyroid tissue (parathyroid adenoma or parathyroid hyperplasia). The presence of parathyroid adenoma or parathyroid hyperplasia was documented by histopathologic examination. In 3 dogs with hypercalcemia of malignancy, parathyroid scintigraphy was negative for hyperfunctioning parathyroid tissue and the scans were classified as true negative. Parathyroid scintigraphy correctly identified the presence and location of hyperfunctioning parathyroid tissue in only 1 of 6 dogs with a parathyroid adenoma. False positive and false negative results occurred in dogs with parathyroid adenomas. Parathyroid scintigraphy failed to detect hyperfunctioning parathyroid tissue in 5 of 6 dogs with parathyroid hyperplasia and were classified as false negative. False positive results were obtained in the remaining dog with parathyroid hyperplasia. Sensitivity of parathyroid scintigraphy for detecting and localizing hyperfunctioning parathyroid tissue was 11%, specificity was 50%, and overall accuracy was 27%. Positive and negative predictive value were 25% and 27%, respectively. Sensitivity for detection of parathyroid adenomas was 25%, and sensitivity for detection of hyperplastic glands was 0 %. Results of this study indicate that double-phase parathyroid scintigraphy does not appear to have acceptable accuracy in detecting hyperfunctioning parathyroid glands in dogs. Due to the poor sensitivity and specificity of the technique in dogs, parathyroid scintigraphy is not recommended for definitive identification of abnormal parathyroid glands as the cause of hypercalcemia in dogs.

Synthesis and evaluation of a new series of 17alpha-[(123)I]iodovinyl estradiols.

A series of 17alpha-substituted estradiols was synthesized in which the stereochemical characteristics of carbons 20 and 21 were modified. It was found that the (Z)-isomer demonstrated more favorable receptor binding affinity than the corresponding (E)-isomer.

Evaluation of plasma time-activity curves of technetium-99m-mebrofenin for measurement of hepatic function in dogs.

In this study, plasma time-activity curves of 99mTc-mebrofenin were used to quantify hepatic function in dogs before and after induction of hepatic damage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minutes following a peripheral venous injection of 111-222 MBq (3-6 mCi) of 99mTc-mebrofenin. The area under the plasma time-activity curve (AUC) was calculated using two different methods and compared to direct measurement of the hepatic extraction efficiency. First pass hepatic extraction efficiency of 99mTc-mebrofenin was calculated from differential equation analysis of a two-compartment model following mesenteric venous injection of the radiopharmaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, plasma clearance and hepatic extraction efficiency determination were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IP). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a two compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1-60 minutes (AUC60) had the best correlation with hepatic extraction efficiency (r2 = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis: hepatic extraction efficiency = 105.583 - 3.099 x 10(5) x AUC60. Plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to quantify hepatic function which can be performed without a gamma camera.

Microvascular transplantation of a free omental graft to the distal extremity in dogs.

OBJECTIVE: To assess the survival of a free omental graft applied to an experimentally created wound on the distal extremity in dogs. STUDY DESIGN: A free omental graft was evaluated as a primary method of treatment for dogs with distal extremity wounds in an experimental model. ANIMALS OR SAMPLE POPULATION: Five adult intact female mixed breed dogs weighing 21.8 kg to 25.0 kg. METHODS: A free omental graft was harvested from the abdomen and transferred to a wound bed overlying the medial aspect of the tibia. A microvascular anastomosis was performed between the graft vessels and vessels at the recipient site. Daily clinical assessment of graft viability was performed. Angiography and 99mTechnetium labeled macroaggregated albumin (99mTc MAA) scintigraphic perfusion scans were performed on either day 4, 5, or 7. Postmortem collection of tissues for histopathologic analysis was performed immediately after imaging. Total operative time and graft ischemia time were evaluated for effects on graft survival. RESULTS: Two of seven grafts survived to the end of the study, three of seven grafts failed because of ischemia, and two of seven grafts failed because of self-trauma. There was no clinically significant morbidity associated with the abdominal portion of the procedure. Because of the small number of surviving grafts, the effects of operative time and graft ischemia time could not be statistically evaluated. CONCLUSIONS: Microvascular transplantation of a free omental graft can result in a viable tissue covering of a distal extremity wound, however, the failure rate is unacceptably high. CLINICAL RELEVANCE: A free omental graft may not have sufficient durability to be an acceptable wound covering by itself. Further studies combining omentum with a skin graft or other tissues may result in a clinically useful technique.

Renal nuclear medicine: a review.

Renal nuclear medicine is used to evaluate renal function and morphology. Renal scintigraphy is the best imaging modality for evaluation of functional parameters such as glomerular filtration rate and effective renal plasma flow. The commonly used renal radiopharmaceuticals are reviewed. Both imaging and non-imaging techniques are presented. Specific applications of renal nuclear medicine are discussed.

The use of colonic irrigation to control fecal incontinence in dogs with colostomies.

OBJECTIVE: To determine if once-daily colonic irrigation results in fecal continence for a 24-hour period in dogs with colostomies and if colonic volume increased in response to the irrigation. STUDY DESIGN: A prospective controlled experimental study. ANIMALS: Four intact male and one intact female mixed breed dogs. MATERIALS: All dogs received left end-on paralumbar colostomies. Four dogs received once-daily colonic irrigation for 8 weeks, whereas the control dog did not. Daily fecal weights were recorded for the length of the study in all dogs. Barium enema studies and volumetric studies were used to determine colonic volumes. RESULTS: Daily fecal weights were significantly decreased in treatment dogs compared with the control dog. Colonic volume increased in irrigated dogs in response to daily irrigation over the 8 week period of the study. CONCLUSIONS: Colonic irrigation resulted in significantly decreased fecal production over a 24-hour period. Therefore management of dogs with colostomies would be more practical and cost effective. It did not result in complete fecal continence in this study. Further clinical studies are indicated to determine if longer periods of irrigation would result in complete continence.

The eye and orbit.

Computed tomography (CT) and magnetic resonance imaging (MRI) provide excellent morphological detail of the eye and its associated structures. In veterinary medicine, these imaging modalities are most often used to diagnose and determine the extent of ocular or periocular tumors. They may also be used to diagnose inflammatory conditions of the orbital region and to determine the severity and extent of ocular trauma. This article reviews the applications of CT and MRI for ocular and orbital diseases, discusses normal findings, and presents representative case examples.

Radiographic, histologic, and cytologic lesions associated with mutations in the fitness1(4226SB) locus of mice.

BACKGROUND AND PURPOSE: Previous investigation of fitness1(4226SB) mice revealed growth retardation and microcytic, hypochromic anemia with functional iron deficiency. Serum biochemical analysis suggested protein-losing enteropathy and liver dysfunction. METHODS: Radiography was done to assess lumbar bone lesions in mice hemizygous for fitness1 (fit1) [c fit1(4226SB/Df(c Mod2 sh1)26DVT] and age-matched sibling controls [c(ch)+/c(ch)+] at 40 or 60 days of age. Macroscopic and microscopic lesions were evaluated at necropsy. Bone marrow was examined cytologically to evaluate hematopoietic lesions. RESULTS: Mice hemizygous for fit1 had radiographically evident lumbar vertebral abnormalities, including various degrees of vertebral body fusion, with loss of intervertebral disk spaces and mild, generalized osteopenia. All mutant mice had scoliosis. Several mutant mice had lordosis and/or kyphosis of variable severity and mild subluxation at the lumbosacral junction. Marked splenomegaly and mild cardiomegaly were evident, and bone marrow color ranged from normal to slightly pale. The spleen had marked extramedullary hematopoiesis; lumbar vertebrae contained microscopic lesions that corresponded to the radiographic lesions. Cytologic examination of bone marrow revealed normocellular to hypocellular status, with mild to moderate erythroid hypoplasia characterized by mild increase in the myeloid-to-erythroid cell ratio, decreased percentage of erythroid precursors, and slight increase in percentage of myeloid precursor cells. CONCLUSIONS: Mutations in fit1 directly or indirectly cause alteration(s) in blood, organs of hematopoiesis (bone marrow, spleen, and liver), heart, and vertebral column, and suggest that this mouse may be a good model for study of scoliosis and relationships between iron metabolism and bone growth.

Evaluation of renal hemodynamics in awake and isoflurane-anesthetized cats with pulsed-wave Doppler and quantitative renal scintigraphy.

The feasibility and reproducibility of obtaining the pulsed-wave Doppler measurements of resistive index (RI) and pulsatility index (PI) were investigated in intrarenal arteries of normal, nonsedated cats, and cats anesthetized with isoflurane. In addition, relative renal function and relative renal blood flow were evaluated using quantitative renal scintigraphy. The percentage of injected dose uptake, time to peak activity, and two indices of renal blood flow (K/A ratio and flow index) obtained during the first pass of 99mTc-MAG3, were determined for both awake and anesthetized cats. Results indicate that measuring RI and PI in nonsedated cats is readily accomplished and that the results are reproducible within an animal. Mean RI and PI values in the awake cats were 0.55 and 0.8, respectively. Significant differences between the awake and anesthetized cats were found for all pulsed-wave Doppler and quantitative renal scintigraphic measurements evaluated.

Quantitative assessment of surgically induced mitral regurgitation using radionuclide ventriculography and first pass radionuclide angiography.

Radionuclide ventriculography has been used in humans to evaluate valvular incompetency. The stroke volume ratio, derived from the radionuclide ventriculogram, is used to quantify the severity of mitral regurgitation (MR). Previous studies conducted in humans have shown that left to right stroke volume ratio increases as the severity of MR increases. In this study, we evaluated radionuclide ventriculography as a noninvasive method to detect MR in dogs with surgically created mitral insufficiency. Six male and three female adult, conditioned mongrel dogs were used. Scintigraphic studies were performed prior to and 4 weeks after surgically created MR. Because of the overlap of the left and right ventricles when viewed from a left lateral position, we combined data from a first-pass radionuclide angiocardiogram with the radionuclide ventriculogram to obtain a corrected stroke volume ratio. Blood flow transit parameters were also derived from the first-pass radionuclide angiocardiogram. Standard left ventricular functional indices were also measured from the radionuclide ventriculogram. On the left lateral view of the heart, 25 to 30% of the right ventricular volume overlaps the left ventricle. After correcting for the overlap, the stroke volume ratio of normal dogs was 1.17+/-0.178 (mean+/-SD), which increased to 2.06+/-0.41 (mean+/-SD) (p < .001) 4 weeks after creation of MR. The was no significant change in left ventricular ejection fraction or peak rate of ejection following MR. The transit times of blood through the left ventricle were measured from the first-pass radionuclide angiocardiogram and were expressed as half-time clearance, peak clearance rate, and time to peak clearance rate. The baseline half-time clearance was 2.07+/-0.71 s (mean+/-SD), which increased to 6.70+/-4.89 s (mean+/-SD) (p = .02) after creation of MR. The baseline peak clearance rate was 49.75+/-8.96 cts/s (mean+/-SD), which decreased to 23.12+/-6.84 cts/s (mean+/-SD) (p < .001) after creation of MR. Stroke volume ratios significantly increased following creation of MR. Blood flow transit through the left ventricle slowed following creation of MR. The variability of these parameters were small in the baseline studies, suggesting these techniques may be clinically useful to gauge the severity of MR in dogs.

Validation of deconvolutional analysis for the measurement of hepatic function in dogs with toxic-induced liver disease.

The extraction of the hepatobiliary radiopharmaceutical 99mTc-mebrofenin (Choletec) by the liver can be used to evaluate the severity of hepatocellular disease. The hepatic parenchymal cells extract mebrofenin from the blood by the same active transport mechanism as bilirubin. The ability of the liver to extract 99mTc-mebrofenin is a measure of hepatic parenchymal cell function. In this study, we induced hepatocellular disease by administration of a hepatotoxic drug and compared a direct method of determining the hepatic extraction of 99mTc-mebrofenin to hepatic extraction fraction derived from deconvolutional analysis. We also compared both methods of calculating the hepatic extraction of 99mTc-mebrofenin to liver histopathology. Hepatic extraction fraction derived from deconvolutional analysis correlated very well to the direct measurement technique (R=0.922, p < 0.001). Both methods of determining hepatic extraction correlated well to quantitative histopathology, having the same correlation coefficient and p values. (R=-0.833, p=0.003). As the hepatic extraction 99mTc-mebrofenin decreased, the severity of the histopathologic lesions of the liver increased in a linear fashion. There was a significant correlation of the hepatic excretion T1/2 to quantitative histopathology (R=0.949, p < 0.001). The hepatic excretion T1/2 increased as the severity of the histopathologic lesions of the liver increased. Hepatic extraction (HEF) and excretion of 99mTc-mebrofenin are good predictors of the severity of hepatocellular damage in toxic induced liver disease. This study helps validate the premise that HEF derived from deconvolutional analysis is a good predictor of the actual first pass hepatic extraction of 99mTc-mebrofenin.

Hepatic extraction efficiency of technetium-99m-mebrofenin in the dog with toxic-induced acute liver disease.

UNLABELLED: Extraction of the hepatobiliary radiopharmaceutical 99mTc-N-(3-bromo-2,4,6-trimethyacetanilide) iminodiacetic acid (mebrofenin; Choletec, Squibb Diagnostic, Princeton, NJ) by the liver may be used as an index of hepatocellular function. The hepatic parenchymal cells extract mebrofenin from the blood using the same active transport mechanism as bilirubin. METHODS: In this study, we induced hepatocellular disease by administering a hepatotoxic drug and compared the hepatic extraction efficiency (HEE), measured directly from an afferent injection of 99mTc-mebrofenin, to quantitative histopathology and to serum biochemistry analysis. RESULTS: The baseline HEE was 95.9% +/- 2.71% (mean +/- s.d.). Dogs that were affected by the hepatotoxic drug had reduced HEE. HEE correlated well to the severity of histologic lesions (r = -0.83, p = 0.003). HEE also correlated well to the increases in the activities of alanine aminotransferase (ALT; r = -0.85, p = 0.002) and aspartate aminotransferase (AST; r = -0.89, p = <0.001), the concentration of fasting bile acid (r = -0.97, p = <0.001), bilirubin (r = -0.92, p = <0.001) and, to a lesser degree, to the activities of alkaline phosphatase (Alk Phos; r = -0.73, p = 0.016). HEE had higher correlation coefficients to the serum biochemistry analysis than did the quantitative liver histopathology. CONCLUSION: Hepatic extraction of 99mTc-mebrofenin is a good predictor of the severity of hepatocellular damage in toxic-induced liver disease.