Judith L. Chezmar

Hepatic iron overload: diagnosis and quantification by noninvasive imaging.

The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscle signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy > 600 Μg/ 100 mg liver dry weight detected on the basis of L/M <0.6 or CT attenuation >70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload.We conclude that MR and CT are sensitive techniques for noninvasive detection of severe hepatic iron overload, with MR providing greater specificity than CT. Lesser degrees of iron deposition, however, may go undetected by our current imaging techniques.

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‐term1 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 μmol/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. J. Magn. Reson. Imaging 2000;12:186–197.

Hepatic arterial resistive indices: correlation with the severity of cirrhosis.

Forty-three patients who were scheduled to undergo a percutaneous liver biopsy were evaluated with Doppler sonography to determine the hepatic arterial resistive index (RI). The histologic specimens were graded by a pathologist regarding cirrhosis and inflammation. The specimens demonstrated no cirrhosis in 12 of 43 (28%) patients, early cirrhosis in 10 of 43 (23%), and established cirrhosis in 21 of 43 (49%). Analysis also revealed that inflammation was absent in three of 43 (7%) patients, minimal in seven of 43 (16%), mild in 17 of 43 (40%), moderate in 13 of 43 (30%), and severe in three of 43 (7%). Hepatic artery RIs (without correction for heart rate) ranged from 0.64+0.06 in patients with early cirrhosis to 0.68 ±0.09 in patients with severe inflammation. There was no significant correlation between the degree of cirrhosis and/or inflammation and hepatic artery RI (with or without correction for heart rate). We conclude that Doppler determination of hepatic artery RIs is not a reliable method of predicting the severity of hepatic cirrhosis and/or inflammation.

Manganese Dipyridoxyl Diphosphate: Effect of Dose, Time, and Pulse Sequence on Hepatic Enhancement in Rats

We used an animal model to investigate the hepatic enhancement characteristics of manganese dipyridoxyl diphosphate (MnDPDP) related to time, dose, and pulse sequence. The contrast doses selected were in the human tolerance range. Using an SE 300/15 pulse sequence, maximum mean hepatic enhancement of 45% (8 mumols/kg) and 58% (12 mumols/kg) over baseline was seen during a plateau maintained between 5 and 50 minutes postinjection in the 8 mumols/kg group, and between 10 and 90 minutes in the 12 mumols/kg group. This plateau was followed by a very gradual decline in hepatic enhancement. Using either 4 or 8 mumols/kg, there was a significant increase in postcontrast hepatic intensity on all relatively T1-weighted pulse sequences (spin echo [SE] 300/15, inversion recovery [IR] 1400/20/400, gradient echo [GE] 47/13/80 degrees, and GE 60/20/30 degrees) except GE 47/13/80 degrees at 4 mumols/kg. At 8 mumols/kg there was superior enhancement, with IR 1400/20/400 and SE 300/15, but at 4 mumols/kg there was no consistently superior sequence. None of the relatively T2-weighted pulse sequences (SE 2000/50, SE 2000/100, or GE 100/30/20 degrees) demonstrated a significant change in hepatic intensity using either dose of contrast. The data suggest that the best combination of dose, pulse sequence, and time for hepatic imaging with MnDPDP is 8 mumols/kg using heavily T1-weighted sequences 5 to 60 minutes following contrast administration.

Magnetic resonance imaging of the pancreas with gadolinium-DTPA.

Gadolinium (Gd)-DTPA was evaluated as a contrast agent for magnetic resonance (MR) imaging of the pancreas at 1.5T. Twenty-five patients were imaged with identical gradient-echo (GE) (TR 47, TE 13, 80° pulse angle) and spinecho (SE) (TR 300, TE 15) MR sequences prior to and following an intravenous bolus of 0.1 mmol/kg Gd-DTPA. Marked pancreatic enhancement was demonstrated on dynamic sequential breath-hold GE images obtained immediately following the Gd-DTPA bolus (116% mean enhancement over pre-Gd-DTPA images). Enhancement decreased but persisted on the SE images obtained approximately 5 and 15 min following the Gd-DTPA bolus (65 and 60% mean enhancement, respectively). Five of the patients had a pancreatic mass. In these five patients, the enhancement of pancreatic tissue resulted in improved conspicuity of the mass. These initial results suggest that pancreatic enhancement occurs following an intravenous bolus of Gd-DTPA and has the potential to improve MR visualization of pancreatic masses.

Magnetic resonance imaging in hemochromatosis: extrahepatic iron deposition.

The magnetic resonance (MR) appearance of the liver in hemochromatosis has been previously described. We report a case in which iron deposition in the pancreas, spleen, and lymph nodes is demonstrated by MR.

Incidence of cholelithiasis among patients with cirrhosis and portal hypertension

One hundred and two patients with cirrhosis and portal hypertension were evaluated sonographically to determine the presence or absence of cholelithiasis. The gallbladder was visualized in 80 of 102 patients. Cholelithiasis was present in 43 of 80 cases (54%). All 22 patients in whom the gallbladder was not seen sonographically had had a previous cholecystectomy. Five of them were operated on prior to development of cirrhosis with portal hypertension, but 14 of the remaining 17 (82%) had evidence of cholelithiasis at pathology. Hence, there was an overall incidence of cholelithiasis of 59% among our 97 patients. This study as well as previous autopsy data indicate an increased incidence of cholelithiasis in patients with cirrhosis, irrespective of etiology or sex. The incidence of cholelithiasis in this study, however, was approximately twice that previously reported in cirrhotics at autopsy. Furthermore, patients with portosystemic shunts showed a significantly higher incidence of cholelithiasis compared to patients who were not shunted (68% vs 49%,p=0.028). We believe the severity and duration of cirrhosis in our patient population, all with documented portal hypertension, may be the cause of this increased incidence.

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 (MnDPDP), 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 µmol/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 µmol/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 µmol/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.

Focal Hepatic Lesions: Detection by Dynamic and Delayed Computed Tomography Versus Short TE(TR Spin Echo and Fast Field Echo Magnetic Resonance Imaging

Eighteen patients with focal hepatic lesions were evaluated with two computed tomographic (CT) techniques including dynamic sequential bolus contrast CT and delayed contrast CT, and 3 magnetic resonance (MR) techniques including a spin echo pulse sequence with TE/TR of 21/310 msec and 2 fast field echo sequences using a TE/TR of 15/300 msec and 80° flip angle (T1-weighted) and TE/TR of 15/500 msec and 10–20° flip angle (T2-weighted). We concluded that CT, using delayed contrast and dynamic sequential bolus contrast techniques, was consistently superior to the 3 MR pulse sequences used on our imagers in terms of number of lesions detected, lesion-to-liver contrast, and quality of scan.

Delayed magnetic resonance hepatic imaging with gadolinium-DTPA.

Magnetic resonance imaging of the liver was performed on 11 rabbits (3-5 kg) before and at 4, 5 and 6 hours after the intravenous administration of 0.3 mM/kg Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) to determine if hepatocytes exhibit delayed excretion of Gd-DTPA, similar to the delayed hepatic excretion of iodinated contrast agents. Imaging was performed at 0.5 Tesla in the axial plane using a spin echo sequence of TR/TE, 250/20 milliseconds. Precontrast and postcontrast intensity changes for liver and muscle were standardized and compared over time. The average percent of postcontrast enhancement for liver and muscle, respectively was: 30.6 +/- 9.5% and 17.3 +/- 17.0% immediately postcontrast; 9.7 +/- 13.6% and 1.6 +/- 13.8% at 4 hours; 9.6 +/- 7.8% and 4.3 +/- 13.2% at 5 hours; and 11.0 +/- 7.8% and 4.1 +/- 11.7% at 6 hours. We conclude that there is not significant hepatocyte excretion of Gd-DTPA at 4 to 6 hours postcontrast injection in rabbits and that this may not be an advantageous paramagnetic contrast strategy for focal hepatic lesion detection.