Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

Extravasation detection accessory: clinical evaluation in 500 patients.

PURPOSE: To assess the ability of an extravasation detection accessory (EDA) to detect clinically important (> or = 10 mL) extravascular injection of iodinated contrast material delivered with an automated power injector. MATERIALS AND METHODS: Five hundred patients referred for contrast material-enhanced body computed tomography (CT) participated in a prospective, multi-institutional, observational study in which the EDA was used to identify and interrupt any injection associated with clinically important extravasation. The presence or absence of extravasation was definitively established with helical CT at the injection site (injection rate, from 1.0 to 5.0 mL/sec; mean, 2.9 mL/sec; median, 3.0 mL/sec). RESULTS: There were four true-positive (extravasation volumes, 13-18 mL), 484 true-negative, 12 false-positive, and no false-negative cases. The prevalence of overall and clinically important (> or = 10 mL) extravasation was 3.6% (18 of 500 cases) and 0.8% (four of 500 cases), respectively. The EDA had a sensitivity of 100% (four of four cases; 95% CI: 51%, 100%) and a specificity of 98% (484 of 496 cases; 95% CI: 96%, 99%) in the detection of clinically important extravasation. CONCLUSION: The EDA is easy to use, safe, and accurate in the monitoring of intravenous injections for extravasation, which could prove especially useful in high-flow-rate CT applications.

Contrast media extravasation during dynamic CT: detection with an extravasation detection accessory.

To detect extravasation of contrast media during mechanical power injection at dynamic computed tomography, a 5 x 8-cm pliable adhesive patch was applied to the skin over the intravenous cannula and connected to the power injector with a cable to monitor electrical skin impedance. If the rate of change or the slope of impedance over time indicated an extravasation event, the power injector was set into a pause mode. In animal and human studies, monitoring with the device was successful. Extravasation of ionic contrast agents decreased impedance and that of nonionic agents increased impedance.

A multicenter clinical trial of Gadolite Oral Suspension as a contrast agent for MRI.

The purpose of this study was to assess the effectiveness and safety of Gadolite Oral Suspension as a gastrointestinal (GI) contrast agent for MRI in a phase II and two phase III multicenter clinical trials. Gadolite was administered to 306 patients with known or suspected abdominal and/or pelvic disease. MRI with T1- and T2-weighted sequences was performed before and after ingestion. Efficacy was evaluated by having two masked readers rate the certainty of their MR diagnosis (0 = uncertain, 1 = probable, 2 = definite) on randomly presented pre- and post-Gadolite Oral Suspension enhanced images. Principal investigators also evaluated the images and established the final diagnosis. Vital signs, clinical chemistries, and adverse events were documented. Blood and urine samples were analyzed for gadolinium content to determine whether Gadolite Oral Suspension was absorbed systemically. Certainty in MR diagnosis increased significantly (P < .001) for both blinded readers between pre- and post-Gadolite images (.49-1.18 for reader 1: .46-1.53 for reader 2). Sensitivity, specificity, and accuracy also increased for both masked readers. No gadolinium was detected in blood or urine samples. There were no serious adverse events and no apparent drug-related trends in mean vital signs or laboratory values. Gadolite is a highly effective, safe, and well tolerated contrast agent for clinical use with MRI.

Hepatic metastases.

Metastatic disease is the most common cause of malignant liver lesion in the United States. This article focuses on the MR techniques utilized for evaluation of the liver for metastatic disease, the MR appearance of hepatic metastases, and several contrast agents being developed to further improve detection of focal hepatic lesions by MR imaging.

Adrenal gland enhancement at MR imaging with Mn-DPDP.

PURPOSE: To determine adrenal gland enhancement with manganese (II) N,N' dipyridoxylethylenediamine-N,N'-diacetate 5,5'bis(phosphate) (DPDP) at magnetic resonance imaging. MATERIALS AND METHODS: After phase III trials, fat-suppressed, motion-compensated, T1-weighted spin-echo images (repetition time, 500 msec; echo time, 12 msec) of 13 consecutive patients were obtained at 1.5 T at one site, prior to and approximately 30 minutes after intravenous administration of 5 mumol/kg Mn-DPDP. Images were analyzed visually and by means of region-of-interest measurements, normalized to spleen. With data added from three more sites, enhancement of three adrenal adenomas and two metastases was analyzed. RESULTS: Twenty-five of 26 adrenal glands were depicted on MR images, and all showed enhancement. Mean adrenal enhancement (38%) was comparable to mean enhancement of liver (46%), pancreas (25%), and renal cortex (58%). Adrenal cortex and medulla could not be distinguished in nonenhanced or enhanced images. All three adrenal adenomas enhanced by more than 40%, but the metastases did not enhance. CONCLUSION: Functioning adrenal tissue (glands and at least some adenomas) are enhanced with Mn-DPDP.

Recurrent tumor after resection of hepatic metastases from colorectal carcinoma: location and time of discovery as determined by CT.

OBJECTIVE: Despite studies showing increased survival rates for patients after surgical resection of hepatic metastases, recurrences occur in 75% of treated patients. The purpose of this study was to determine the location and time of discovery of recurrent tumor on CT scans after resection of hepatic metastases from colorectal carcinoma. MATERIALS AND METHODS: In a 6-year period, 32 patients (16 men and 16 women) who had undergone partial hepatic resection for colorectal metastases had follow-up CT at our institution. A total of 125 CT examinations of the chest and abdomen were retrospectively reviewed for the presence and location of recurrent disease. Recurrence was either confirmed by biopsy (n = 12) or presumed on the basis of growth of new lesions (n = 17). RESULTS: With a mean follow-up of 22 months (range, 1-60 months), recurrence was found at 29 sites in 25 patients. Thirteen sites were hepatic, and 16 were extrahepatic. Three patients had both hepatic and pulmonary disease. Recurrence within the liver was away from surgical margins in 11 (85%) of 13 patients at 14 +/- 7 months and adjacent to a surgical margin in the remaining two patients (15%) at 17 +/- 1 months. Extrahepatic recurrences were discovered in the lung in 11 (69%) of 16 patients at 21 +/- 12 months; in an adrenal gland in two patients (13%) at 19 +/- 5 months; in lymph nodes of the porta hepatis in one patient (6%) at 11 months; at the primary colonic anastomosis in one patient (6%) at 3 months; and in a retroperitoneal lymph node in the remaining patient (6%) at 12 months. CONCLUSION: Surgery was effective in treating the preoperatively detected hepatic metastases. Only two of 25 patients had recurrence related to a hepatic surgical margin. Most recurrences occur more than 1 year after surgery, most often in lung or liver away from surgical margins, and they probably represent small metastases undetectable with current preoperative or intraoperative techniques.

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.

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.

Splenic venous flow exceeding portal venous flow at Doppler sonography: relationship to portosystemic varices.

OBJECTIVE: The purpose of this study was to determine if the Doppler sonographic finding of hepatopetal flow in the splenic vein that exceeds hepatopetal flow in the portal vein is associated with portosystemic varices. MATERIALS AND METHODS: Sixty-four patients with chronic liver disease were studied retrospectively. In 32 patients, splenic venous flow exceeded portal venous flow (S > P group); in 32 patients, portal venous flow exceeded splenic venous flow (P > S group). All patients were evaluated with Doppler sonography and CT of the upper part of the abdomen. Upper endoscopy was performed within 3 months of sonography in 44 of the 64 patients. RESULTS: In the S > P group, mean splenic volume was significantly larger (p = .02) than in the other group. The prevalence of varices as determined by CT in the esophageal, coronary, and peripancreatic regions was also higher in this group (p < or = .01). When esophageal varices were present, they were judged on the basis of their CT appearance to be massive in 50% of the S > P group and in 0% of the P > S group. Upper endoscopy revealed esophageal varices in 92% of the S > P group and in 55% of the P > S group (p < .005). Bleeding esophageal varices were noted in 75% of the S > P group and in 30% of the P > S group (p < .01). CONCLUSION: Patients with chronic liver disease and the Doppler sonographic finding of splenic venous flow that exceeds portal venous flow have an increased prevalence of portosystemic varices, which tend to be larger and more likely to bleed.

"Keyhole" method for accelerating imaging of contrast agent uptake.

Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeroes for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradient- and spin-echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation.

Malignant hepatic tumors: safety of high-dose percutaneous ethanol ablation therapy.

The authors retrospectively analyzed clinical records to determine the safety and complication rate of percutaneous ethanol ablation therapy with more than 10 mL of ethanol administered per session for treatment of malignant hepatic tumors. Ten patients underwent a total of 35 sessions with 10 mL or more of ethanol, and four underwent 18 sessions with 10 mL or less. No serious complications occurred with any dose. Pain and fever were the most common complications at all doses, and the higher frequency of these at larger ethanol volumes may be related to the greater degree of tumor necrosis induced by the larger volume.

Magnetic resonance imaging after arterial portography with manganese dipyridoxal diphosphate.

RATIONALE AND OBJECTIVES: The authors assess performing hepatic magnetic resonance imaging (MRI) after arterial portography with manganese dipyridoxal diphosphate (MnD-PDP), a hepatobiliary contrast agent, as an invasive but potentially highly sensitive means of focal lesion detection. METHODS: Eight pigs underwent superior mesenteric artery catheterization and injection of 10 mumol/kg MnDPDP. Magnetic resonance imaging at 1.5 T (SE-140/10) was performed before, then at 15 and 30 minutes after injection. Seven or more days later, the same MRI protocol was performed after intravenous injection of 10 mumol/kg MnDPDP. RESULTS: Fifteen minutes after intra-arterial injection, enhancement of the liver predominated (86 +/- 13%), followed by the renal cortex (44 +/- 14%), pancreas (26 +/- 9%), and spleen (14 +/- 9%). At 30 minutes, enhancement of renal cortex significantly increased (50 +/- 14%). There was no significant difference in enhancement of the liver, spleen, pancreas, or renal cortex when we compared intra-arterial and intravenous administration. CONCLUSION: After the injection of 10 mumol/kg MnDPDP into the superior mesenteric artery of pigs there is no significant difference in visceral organ enhancement compared to intravenous administration. The data suggests that the hepatocyte binding sites may be overwhelmed by this dose and/or injection rate of MnDPDP.