A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

Using physician work relative value units to profile surgical packages: methods and results for kidney transplant surgery.

BACKGROUND: This investigation outlines an approach for using the physician work relative value units (RVUs) in the Medicare Fee Schedule (MFS) to profile physician clinical activities. These techniques were then used to profile the physician services associated with kidney transplant patients at Emory University System of Health Care. METHODS: All physician services associated with 179 patients who had kidney transplant surgery in 1993 were studied. By using billing data, physician work RVUs were assigned to each service and the results were analyzed by type of service and the hospital department providing the service for physician work RVUs and physician charges. RESULTS: A mean of 130.4 physician work RVUs were involved in the 179 episodes of care. Surgical services represented 48.7% of the physician work activity in the kidney transplant. Visit and consultative services make up the next highest share with 25.5% of the physician work RVUs, whereas anesthesia makes up 13.3% of physician work RVUs. Physician charges totaled $16,249 for kidney transplants in 1993 dollars. Surgical services accounted for 54.2% of physician charges connected with kidney transplants, whereas visits and consultative services represented 20.6% of physician charges. CONCLUSIONS: Physician work RVUs in the MFS offer a unique and much needed perspective on physician clinical activities. Physician work RVUs are an important new tool for healthcare and researchers and their use needs to be more fully explored and benchmarks developed for all major medical and surgical services.

Gadoteridol-enhanced MR imaging of malignant hepatic tumors: effects of triple versus standard doses on lesion-liver contrast.

OBJECTIVE: The purpose of this study was to compare liver signal-to-noise ratio (SNR), lesion SNR, and lesion-liver contrast-to-noise-ratio (CNR) in patients with malignant liver lesions after the administration of a standard dose (0.1 mmol/kg of body weight) or a triple dose (0.3 mmol/kg) of a gadolinium chelate (gadoteridol). We hypothesized that the higher dose would produce a higher lesion-liver CNR and therefore increase the conspicuity of hepatic lesions. MATERIALS AND METHODS: A total of 85 patients with malignant hepatic masses (61 metastases, 22 hepatocellular carcinomas, and two lymphomas) proved by histologic or follow-up studies underwent MR imaging at 1.5 T. T1-weighted spin-echo imaging and gradient-echo imaging were done before and within 1 min after (gradient echo) as well as 5 (spin echo) and 15 (spin echo) min after the injection of 0.1 or 0.3 mmol of gadoteridol per kg, randomized before the start of the study (39 patients received the standard dose, and 46 received the triple dose). The signal intensities of the liver and lesions and the SD of background noise were measured by use of regions of interest to calculate the SNR of the liver and malignant lesions and the lesion-liver CNR. RESULTS: The lesion-liver CNR was increased significantly at 5 and 15 min after the administration of gadoteridol. No significant differences in the liver SNR, lesion SNR, and lesion-liver CNR (after 1 min: standard dose, -5 +/- 8, and triple dose, -4 +/- 14; after 5 min: standard dose, -1 +/- 5, and triple dose, 2 +/- 8; and after 15 min: standard dose, 1 +/- 5, and triple dose, 6 +/- 20) were found between the doses at all time points. CONCLUSION: Triple-dose gadoteridol does not improve the lesion-liver contrast of malignant hepatic lesions over that provided by the standard dose and is not warranted for liver MR imaging.

Time versus density enhancement of liver, spleen, and great vessels following rapid intravenous infusion of perflubron emulsion.

RATIONALE AND OBJECTIVES: We studied hepatosplenic enhancement in rhesus monkeys for 5 hr after rapid administration of perflubron (perfluorooctyl bromide [PFOB]) in an attempt to determine a clinically useful imaging window. METHODS: Five rhesus monkeys were examined using perflubron emulsion, 90% w/v perfluorochemical administered intravenously at a dose of 1.5 ml/kg and rate of 0.5 ml/sec. Helical computed tomography examination of the abdomen was obtained prior to the contrast bolus and 5 min, 30 min, 1, 2, 3, 4, and 5 hr postcontrast. Mean density of liver, spleen, and aorta was measured at each time interval. RESULTS: Significant aortic enhancement of 53 +/- 7 Hounsfield units (HU) (p < .0001) and liver enhancement of 19 +/- 4 H (p < .0004) occurred after 5 min and did not change significantly (p > .05) over 5 hr. Splenic enhancement of 35 +/- 9 HU was significant at 5 min (p < .0001) and continued to increase for 5 hr. CONCLUSION: Enhancement of the liver, blood vessels, and spleen is rapid and persists for at least 5 hr, which suggests a wider temporal window for hepatosplenic imaging with perflubron than is currently available with iodinated contrast agents.

Safety and optimum concentration of a manganese chloride-based oral MR contrast agent.

To determine the safety of a manganese chloride-based oral magnetic resonance (MR) contrast agent and the ideal concentration of the agent for marking in three different anatomic sites (stomach, middle of the small bowel, and ileocecal region), six healthy volunteers were evaluated before and after administration of 900 mL of three different concentrations of the contrast agent. Images were evaluated subjectively and objectively. No adverse events were noted. There was a minimal rise in manganese blood levels at 6 hours after administration, with a return to baseline at 24 hours. The imaging data demonstrated good-to-excellent bowel marking on T1-weighted images at all three concentrations. However, on T2-weighted images, the 40 mg Mn+2/L concentration provided improved hypointense bowel marking relative to the 20 mg/L concentration. Little difference was seen between the 40 and 60 mg/L concentrations. Fast T1- and T2-weighted sequences provided superior image quality to that of conventional spin-echo sequences.

Perfluoroctyl bromide as a blood pool contrast agent for computed tomographic angiography.

RATIONALE AND OBJECTIVES: We determined whether perfluoroctyl bromide (perflubron) could be used as a computed tomography (CT) angiographic agent by studying vessel visibility (celiac artery, superior mesenteric artery [SMA], and renal arteries) with spiral CT and three-dimensional (3D) reconstructions. METHODS: Five rhesus monkeys were examined with a perflubron emulsion (90% [w/v] perfluorochemical; administered intravenously at a dose of 1.5 ml/kg and at a rate of 0.5 ml/sec. Spiral CT was performed immediately and at 5 hr after injection. Three dimensional images of the aorta at the level of the celiac artery, SMA, and renal arteries were reconstructed and blindly rated 0-4 (0 = not seen; 4 = excellent visualization) by two observers. RESULTS: All the vessels had the best ratings immediately after injection: celiac artery, 2.8 +/- 0.42; SMA, 2.7 +/- 0.48; left renal artery, 2.1 +/- 0.99; and right renal artery, 1.2 +/- 1.03. The ratings after the 5-hr delay were as follows: celiac artery, 1.3 +/- 1.34; SMA, 1.5 +/- 1.08; left renal artery, 1.5 +/- 0.97; and right renal artery, 1.2 +/- 0.79. CONCLUSIONS: Spiral CT angiography with a perflubron emulsion successfully demonstrated all vessels immediately and at 5 hr after contrast agent infusion. Further refinements of the dose, rate, and reconstruction technique are expected to increase vessel visibility over this wide imaging window.

Cost-effective use of low-osmolality contrast media for CT of the liver: evaluation of liver enhancement provided by various doses of iohexol.

OBJECTIVE: Because of pending efforts to reform health care in the United States, judicious use of low-osmolality contrast media is important. We studied the effects of using various concentrations and volumes of iohexol, compared with the conventional dose and concentration of diatrizoate meglumine used for CT, to determine if a more cost-effective dose results in diagnostically efficacious liver enhancement. SUBJECTS AND METHODS: A total of 902 patients received one of nine different doses of IV contrast media. Eight doses of iohexol were used: 125 ml of iohexol 350 (350 mg l/ml, 44 g l/dose), 100 ml of iohexol 350 (35 g l/dose), 150 ml of iohexol 300 (300 mg l/ml, 45 g l/dose), 120 ml of iohexol 300 (36 g l/dose), 100 ml of iohexol 300 (30 g l/dose), 175 ml of iohexol 240 (240 mg l/ml, 42 g l/dose), 150 ml of iohexol 240 (36 g l/dose), and 125 ml of iohexol 240 (30 g l/dose). A single dose (150 ml) of diatrizoate meglumine 60% (w/v) was used (42 g l/dose). Contrast material was injected at a rate of 2 ml/sec. Scanning began 35-45 sec after injection. Quantitative analysis of enhancement was performed by obtaining region-of-interest measurements through the liver on scans obtained before and after injection of contrast material. Mean and maximum changes in hepatic density and mean time to maximum enhancement were measured. Mean time-density curves were subsequently derived for each dose of contrast material. Qualitative analysis of enhancement was performed by using subjective, previously defined criteria. All studies were interpreted in a double-blind fashion. RESULTS: Mean hepatic enhancement was greater with 125 ml of iohexol 350 and 150 ml of iohexol 300 than with other doses of contrast material (p < .05). Both 125 ml of iohexol 350 and 150 ml of iohexol 300 produced actual hepatic enhancement of more than 50 H for over 60 sec. The greatest maximum increase in hepatic density occurred with 125 ml of iohexol 350. When analyzed qualitatively, 150 ml of iohexol 300 resulted in the highest percentage of optimum enhancement. CONCLUSION: According to quantitative analysis, 125 ml of iohexol 350 administered at a rate of 2 ml/sec produces the best enhancement, whereas according to qualitative analysis, 150 ml of iohexol 300 produces the best enhancement. All doses of iohexol 240 provide poor enhancement compared with a conventional dose of contrast material of 150 ml of diatrizoate meglumine 60% or 150 ml of iohexol 300. A moderate cost savings can be achieved by using 125 ml of iohexol 350 for dynamic sequential CT.

Does CTAP prior to hepatic resection improve patient survival rates?

The purpose of our study was to compare survival rates of colon carcinoma patients who had undergone attempted curative hepatic resection based on liver staging by computed tomographic angiography (CTA) or portography (CTAP) with previously reported survival rates of patients who underwent similar surgery without preoperative CTAP evaluations. A total of 404 CTAP studies performed at three institutions were reviewed. Of this group, 197 had colon carcinoma. Sixty-nine of the colon patients went to surgery. Actuarial adjusted yearly survival rates were calculated for the prior CTAP colon group and compared to historical controls. The control survival data were taken from reports published prior to the CTAP era. Our study demonstrated no difference in the 1-year survival data between the groups. However, the CTAP patients had greater survival in years 2-4. This greater survival may be multifactorial but in part due to better surgical selection caused by CTAP.

Contrast-enhanced spiral CT of the liver: effect of different amounts and injection rates of contrast material on early contrast enhancement.

OBJECTIVE: Spiral CT allows rapid hepatic imaging during a single breath-hold. The increase in imaging speed potentially allows contrast material to be used more efficaciously than with conventional dynamic CT, perhaps allowing a decrease in the volume of required contrast agent. To determine how this can be accomplished, we studied the effect of different bolus IV injection rates and amounts of contrast material on early hepatic enhancement during dynamic bolus spiral CT. SUBJECTS AND METHODS: A group of 20 healthy male volunteers were divided into four groups of five each. The groups received 75, 100, 125, or 150 ml of contrast material (Omnipaque 300, 300 mg l/ml). Each person within each group was scanned as contrast material was injected at rates of 3, 4, and 5 ml/sec. Hepatic enhancement was evaluated by comparing quantitative regions of interest before and after bolus injection of contrast material. Variations in enhancement produced by changes in volume and injection rate of contrast material were evaluated on early, middle, and late sections of the spiral, corresponding to 32-34, 41-43, and 51-53 sec, respectively, after the injection of contrast material was begun. RESULTS: Hepatic enhancement increased more rapidly when the bolus of contrast material was given at a rate of 5 ml/sec than at the slower rates of 3 or 4 ml/sec. Enhancement of the liver was greatest at the late portion of the spiral (51-53 sec after start of the bolus injection), averaging 73 and 79 H for volumes of 125 and 150 ml, respectively, at 5 ml/sec, and the enhancement was still increasing at that time. Enhancement curves predict 50- and 70-H mean increases in hepatic attenuation on initial slices with scan delays of approximately 40 and 50 sec, respectively, for these two protocols. CONCLUSION: Our results demonstrate that there is a marked dependence on early hepatic enhancement produced by variations in volume and injection rate of contrast material. We found no difference in the results produced by 125- and 150-ml volumes. These results are important for maximizing the effectiveness of IV contrast material during rapid hepatic spiral CT scanning.

Enhancement effects of a hepatocyte receptor-specific MR contrast agent in an animal model.

The enhancement characteristics of the liver and spleen produced by a hepatocyte-specific magnetic resonance imaging agent, an arabinogalactan-coated ultrasmall superparamagnetic iron oxide derivative, BMS 180550, were evaluated. Both heavily T1- and T2-weighted sequences were used. Imaging was performed in the farm pig model, as a function of contrast agent concentration (5, 10, and 20 mumol of iron per kilogram) and delay (immediate, 0.5, 2.5, 5.0, 7.5, and 9.0 hours) after bolus injection of BMS 180550. BMS 180550 provided excellent contrast enhancement characteristics by producing marked positive enhancement with T1-weighted sequences and marked negative enhancement with T2-weighted sequences. The T1-weighted enhancement immediately after contrast agent injection was of greater magnitude in the spleen (329% +/- 83) than in the liver (66% +/- 16). Postcontrast negative enhancement with T2-weighted sequences was largely hepatocyte specific at 5 and 10 mumol/kg but was also seen within the spleen at 20 mumol/kg. The authors discuss the possible mechanisms that produce these changes and conclude that 10 mumol/kg BMS 180550 is near the optimum dose for maximizing the enhancement properties of this agent with all sequences in the farm pig.

CT angiography and CT arterial portography in evaluation of hepatic adenomas.

OBJECTIVE: Our goal was to evaluate the contribution of CT arterial portography (CTAP) and CT angiography to accurate determination of disease extent in patients with known hepatic adenomas. MATERIALS AND METHODS: Imaging results were reviewed in three women with known hepatic adenomas, all of whom had percutaneous biopsy to confirm the diagnosis. Results of CTAP studies in all patients as well as results of CT arteriography in one patient were compared with routine dynamic CT studies in all three and with MRI studies in two. RESULTS: The CTAP and CT arteriography demonstrated multiple additional lesions in all patients as compared with routine dynamic CT and MRI studies. In one of the patients who was found to have hepatic adenomatosis, the degree of tumor involvement changed the operative procedure from partial hepatectomy to liver transplantation. CONCLUSION: In patients with known hepatic adenomas who require surgery, CTAP provides more accurate preoperative staging of extent of liver replacement with tumor.

Focal liver lesions: characterization with nonenhanced and dynamic contrast material-enhanced MR imaging.

PURPOSE: To evaluate prospectively the diagnostic accuracy of non-enhanced and gadolinium-enhanced magnetic resonance (MR) imaging in characterization of hepatic lesions. MATERIALS AND METHODS: Fifty-five patients with benign and 52 patients with malignant focal liver lesions underwent examination at 1.5 T that comprised nonenhanced and dynamic contrast material-enhanced images. Four experienced radiologists independently read the different sets of images without and with knowledge of clinical history. RESULTS: Receiver operating characteristic analysis showed that dynamic contrast-enhanced MR imaging added information to nonenhanced MR studies and thereby improved distinction between benign and malignant lesions (P < .05). Knowledge of clinical data further improved lesion characterization with nonenhanced and combined nonenhanced and contrast-enhanced MR imaging (P < .05). CONCLUSION: Dynamic contrast-enhanced MR imaging is a useful adjunct for characterization of hepatic lesions. Knowledge of clinical history still has a decisive effect on interpretation of MR images of the liver.

Is the safety of contrast agents an issue in body computed tomography?

RATIONALE AND OBJECTIVES: To investigate the comparative safety profiles of nonionic and ionic contrast agents in body computed tomography (CT) studies. METHODS: A literature search was conducted to examine the following variables: image quality, repeat or aborted studies, and the cost of nonionic agents versus benefits. Data are presented that address the following questions: Does administering nonionic agents save time? Are nonionic agents more likely to provide an adequate study? Does an adequate study necessarily ensure an improved detection rate? RESULTS: The administration of nonionic contrast does not save time during the body CT studies. There is little significant difference between the sensitivity for making a diagnosis when using an ionic or nonionic agent. CONCLUSION: The lack of difference in diagnostic sensitivity or time to perform a study between ionic and nonionic agents does not warrant the conversion to nonionic agents in body CT.

Combined CT arterial portography and CT hepatic angiography for evaluation of the hepatic resection candidate. Work in progress.

PURPOSE: To determine whether the addition of computed tomographic (CT) angiography to CT arterial portography would improve lesion detection and heighten confidence in interpreting perfusion abnormalities. MATERIALS AND METHODS: The two examinations were performed sequentially in 10 candidates for surgical resection of hepatic tumors. Arterial vascular access was obtained with bilateral punctures of the common femoral artery and selective placement of angiographic catheters in the hepatic artery and superior mesenteric artery (SMA). CT scans were obtained first during injection of contrast material into the SMA, followed by repeated imaging of the liver during injection of contrast material into the hepatic artery. RESULTS: The procedure demonstrated, among other results, three additional lesions in two patients, a possibly nontumorous abnormality as tumorous in one, and a suspected tumorous abnormality as nontumorous in one. Suspected nontumorous abnormalities in four patients were confirmed at CT angiography. CONCLUSION: These preliminary data support a trial of this technique in a larger population.

Contrast-enhanced MR imaging of hepatic lesions treated with percutaneous ethanol ablation therapy.

PURPOSE: Magnetic resonance (MR) images were correlated with results of fine-needle aspiration (FNA) to determine the role of MR imaging in evaluating hepatic neoplasms treated with percutaneous ethanol ablation therapy (PEAT). MATERIALS AND METHODS: Contrast material-enhanced and unenhanced MR images were obtained in 11 patients with hepatic neoplasms before PEAT (13 studies) and at intervals after PEAT (25 studies). FNA was performed at each follow-up visit. RESULTS: After PEAT, the MR appearance of the lesions was extremely variable. Also, the signal characteristics of most lesions did not change significantly with any sequence over time. Of eight lesions that demonstrated contrast enhancement before therapy, four demonstrated persistent enhancement and four showed loss of enhancement. Six of these lesions had no viable tumor at FNA. T2-weighted sequences most often showed mixed signal intensity regardless of T2-weighted imaging appearance before therapy. CONCLUSION: The MR appearance of PEAT-treated hepatic lesions is not a reliable indicator of residual or recurrent tumor.

Preoperative determination of the resectability of hepatic tumors: efficacy of CT during arterial portography.

OBJECTIVE: A multiinstitutional study was performed to evaluate the efficacy of CT during arterial portography for determining the resectability of hepatic tumors. The impact of findings from CT during arterial portography on patients' treatment (i.e., surgical vs nonsurgical) was assessed. In patients considered to have resectable tumors, the accuracy of CT during arterial portography for predicting surgical findings was also evaluated. MATERIALS AND METHODS: A retrospective study was done of 404 patients from three institutions who had CT during arterial portography during the period 1985-1991 as part of preoperative staging to determine the resectability of hepatic tumors. The tumors included metastases from colorectal carcinoma in 197 patients (49%); other hepatic metastases, mostly from adenocarcinoma of the stomach, pancreas, and biliary tree in 123 (30%); and primary hepatocellular carcinoma in 84 (21%). Imaging results were correlated with results of percutaneous biopsy of at least one hepatic lesion in patients whose tumors were considered unresectable. In patients whose tumors were considered resectable, results were correlated with preoperative percutaneous biopsy (obtained in almost all cases) and pathologic examination of a surgical specimen (all cases). Although each case was considered individually, four criteria were used for resectability: (1) accessibility of all lesions to lobar or wedge resection that would yield clear margins, (2) anticipation that residual liver tissue after resection would provide sufficient function, (3) the absence of invasion of central hepatic vascular or biliary structures, and (4) the absence of extrahepatic disease. No specific restriction was made with respect to the number of hepatic lesions present. The accuracy of findings by CT during arterial portography for predicting resectability was assessed in the 146 patients who had tumors that were considered resectable on the basis of imaging findings and had surgery. RESULTS: Of 404 patients, only 146 (36%) were thought to be candidates for resection on the basis of findings from CT during arterial portography. Of these, 122 (84%) actually had resection. The 24 patients who did not have resection included 22 patients with disease understaged or overstaged by CT during arterial portography, one with true-negative findings by CT during arterial portography, and one who died during surgery. The accuracy of findings by CT during arterial portography for predicting results at surgery was 85% for all patients and 91% for the subset of patients who had primary colorectal tumors with hepatic metastases. CONCLUSION: Our experience shows that CT during arterial portography is a useful procedure for assessing the resectability of hepatic tumors. In our study, 64% of patients were spared unnecessary surgery.(ABSTRACT TRUNCATED AT 400 WORDS)