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Mononuclear subsets in the peripheral blood of multiple sclerosis patients in relation to results of brain gadolinium- enhancing imaging.

UNLABELLED: Very little is known about processes which are leading to the development of new multiple sclerosis (MS) plaques. Therefore, the problem of correlating immunological disequilibrium in MS patients with the onset of a relapse and with other markers of the disease seems to be of great importance. In our studies we have evaluated the mononuclear subsets in the peripheral blood of multiple sclerosis patients in relation to results of brain gadolinium-enhancing imaging. A positive magnetic resonance imaging (MRI) gadolinium enhancement indicates an ongoing inflammation and activity of the MS process, whereas gadolinium (Gd) negative imaging should be considered as a sign of stabilization of the MS process. MATERIAL AND METHODS: Peripheral blood was taken from 70 MS patients, fulfilling the criteria of McDonald et al [8]. Brain MRI was performed using a Magneton Impact 1.0 T (Siemens) machine. Enhanced T1 images were obtained after administration of 0.1 mmol/kg gadolinium - DTPA. Lymphocyte subsets were analyzed by flow cytometry with the aid of specific monoclonal antibodies. RESULTS: The relative percentage of the white blood cell count as well as the absolute number of mononuclears and of CD3+ lymphocyte were significantly lowered only in the group of gadolinium negative MS cases. The CD4+ relative percentage was significantly higher both in the total as well as in gadolinium positive and negative subgroups. The ratio of CD4/CD8 was significantly higher in MS patients. The absolute number of CD4 lymphocytes was the lowest in gadolinium negative MS cases. CONCLUSION: An appropriate regulation of the Th /T helper/ cells seems to be critical in the control and prevention of diverse states of the disease. In the course of an acute process, gadolinium positive imaging as well as immunological events, represented by mononuclear subsets in the peripheral blood may proceed and change very quickly, whereas gadolinium negative findings reflecting a stabilization of processes, are changing more slowly and therefore may be detected more easily in peripheral blood cell counts.

Adult↗

Gadolinium-enhanced magnetic resonance imaging in acute myocardial infarction.

To evaluate the usefulness of the paramagnetic contrast agent Gadolinium-DTPA (diethylenetriaminepentaacetic acid) in Magnetic Resonance Imaging of acute myocardial infarction, we studied a total of 45 patients with a first acute myocardial infarction by ECG-gated magnetic resonance imaging before and after intravenous administration of 0.1 mmol/kg Gadolinium-DTPA. All patients received thrombolytic treatment by intravenous streptokinase. The magnetic resonance imaging studies were performed after a mean of 88 h (range 15-241) after the acute onset of acute myocardial infarction. Five patients without evidence of cardiac disease served as controls. Spin-echo measurements (TE 30 ms) were made using a Philips Gyroscan (0.5 Tesla) or a Teslacon II (0.6 Tesla). The 45 patients were divided into four groups of patients. In Group I (5 patients) Gadolinium-DTPA improved the detection of myocardial infarction by Gadolinium-DTPA. In Group II (20 patients) the magnetic resonance imaging procedure was repeated every 10 min for up to 40 min following administration of Gadolinium-DTPA. Optimal contrast enhancement was obtained 20-25 min after Gadolinium-DTPA. In Group III (27 patients) signal intensities were significantly higher in the patients who underwent the magnetic resonance imaging study more than 72 h (mean 120) after the acute event, suggesting increased accumulation of Gadolinium-DTPA in a more advanced stage of the infarction process. In Group IV (45 patients) Gadolinium-DTPA was administered in an attempt to distinguish between reperfused and nonreperfused myocardial areas after thrombolytic treatment for acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical feasibility of free-breathing, gadolinium-enhanced magnetic resonance angiography for assessing extracardiac thoracic vascular abnormalities in young children with congenital heart diseases.

OBJECTIVE: Congenital heart diseases in pediatric patients are associated with a wide variety of extracardiac thoracic vascular abnormalities. This study analyzed the value of gadolinium-enhanced magnetic resonance angiography during quiet free breathing for assessing extracardiac thoracic vascular abnormalities in young children with congenital heart diseases. METHODS: Fifty-three children with congenital heart diseases (age range, 1 day-40 months; mean, 10.9 months) associated with extracardiac thoracic vascular abnormalities who had undergone both free-breathing, gadolinium-enhanced magnetic resonance angiography and cardiac catheterization, surgical intervention, or both within 2 weeks were reviewed. Diagnostic findings on gadolinium-enhanced magnetic resonance angiography among patients grouped according to 3 major conditions of conotruncal abnormalities (n = 33), aortic or venous abnormalities (n = 11), and pulmonary vascular abnormalities (n = 9), as well as associated extracardiac thoracic vascular abnormality findings, were compared with findings made by using cardiac catheterization, surgical intervention, or both. RESULTS: Extracardiac thoracic vascular abnormality findings on gadolinium-enhanced magnetic resonance angiography were similar to those on catheterization, surgical intervention, or both in patients with conotruncal abnormalities (124 vs 127, P = .083), aortic or venous abnormalities (36 vs 33, P = .083), and pulmonary vascular abnormalities (24 vs 25, P = .317). The overall sensitivity of gadolinium-enhanced magnetic resonance angiography for detection of these lesions identified by means of catheterization, surgical intervention, or both was 97.9%. However, gadolinium-enhanced magnetic resonance angiography revealed 11 additional extracardiac thoracic vascular abnormalities that were not found on cardiac catheterization. The kappa coefficient for the correlation of image quality and diagnostic value of gadolinium-enhanced magnetic resonance angiography by using a 4-point-scale (1 = nondiagnostic to 4 = excellent) assessed by 2 independent reviewers was excellent (mean score = 3.66), with superb interobserver agreement (kappa = 0.727-0.874). CONCLUSIONS: Free-breathing, gadolinium-enhanced magnetic resonance angiography is clinically feasible for detailed anatomic delineation and treatment planning of various extracardiac thoracic vascular abnormalities in young children with congenital heart diseases.

Cardiovascular Abnormalities↗

Gadolinium-enhanced three-dimensional MR angiography of the aorta and peripheral arteries: evaluation of a multistation examination using two gadopentetate dimeglumine infusions.

OBJECTIVE: Three-dimensional gadolinium-enhanced MR angiography is a rapid and accurate method that can at times image only a limited amount of anatomy during an examination. We evaluated a technique that doubled the anatomy imaged by obtaining two separate gadolinium-enhanced MR angiograms during a single examination. MATERIALS AND METHODS: Twenty-three patients referred for MR evaluation of aortic or peripheral vascular disease underwent two successive gadolinium-enhanced three-dimensional MR angiographic examinations during a single MR examination. An injection of 15 ml of gadopentetate dimeglumine was used for the first MR angiogram, and 25 ml was used for the second MR angiogram. The angiograms were quantitatively and qualitatively evaluated to determine the effect of residual gadolinium from the initial MR angiogram on the second angiogram. RESULTS: The two studies depicted either the entire aorta to the femoral arteries (n = 10) or the distal aorta to the popliteal arteries (n = 13). The total mean gadolinium dose was 0.245 mmol/kg per patient. An average of 15 min elapsed between injections. The value of arterial signal-to-noise ratio (mean, 48.8 versus 56.4) and artery-to-vein contrast-to-noise ratio (mean, 45.5 versus 49.0) increased between the first and second angiograms, respectively. Residual gadolinium elevated the values for venous signal-to-noise ratio (mean, 2.3 versus 7.2) and background-to-muscle signal-to-noise ratio (mean, 5.5 versus 10.1) on the second MR angiogram. Qualitative evaluation by three observers showed no significant differences in diagnostic usefulness or overall image quality between the first and second MR angiograms. CONCLUSION: The use of two low-dose gadolinium-enhanced three-dimensional MR angiograms during a single examination is a feasible approach to increase anatomic coverage when performing gadolinium-enhanced three-dimensional MR angiography of the aorta and peripheral vessels. Although background enhancement is slightly elevated on the second angiogram, such enhancement does not significantly change diagnostic usefulness or overall image quality.

Aged↗

MR imaging of musculoskeletal tumors and tumor mimickers with intravenous gadolinium: experience with 242 patients.

PURPOSE: This pictorial essay reviews our experience with MR scans with gadolinium in patients with musculoskeletal tumors and tumor mimickers. DESIGN: Review of 242 MR scans obtained in the initial evaluation of a possible primary musculoskeletal neoplasm. All scans included a T1-weighted, fat-suppressed sequence following intravenous administration of gadolinium. RESULTS: MR scans with gadolinium did not contribute to differential diagnosis or patient management in 89% of the patients in this series. However, intravenous gadolinium did assist in guiding the biopsy of bulky lesions and evaluating treated tumor beds for possible recurrence. MR scans with gadolinium were sometimes helpful when the differential diagnosis included synovitis, Morton's neuroma or intramuscular myxoma, and when it was important to differentiate cystic from solid lesions. CONCLUSIONS: Routine use of gadolinium in every initial MR examination of a possible musculoskeletal mass is not warranted. However, there are appropriate selected indications for gadolinium administration as outlined above.

Adolescent↗

Toxicological assessment of gadolinium release from contrast media.

In vivo gadolinium release was evaluated for MultiHance, Omniscan and Gadovist estimating gadolinium content in liver, kidneys, spleen, femur and brain after single or repeated intravenous administrations to rats at 1 mmol/kg. Gadolinium acetate (GdAc) at a daily dose of 0.03 mmol/kg and physiological saline were used as positive and negative controls, respectively. No changes in blood chemistry, haematology nor histopathology were seen with any of the tested contrast media, whereas an increase in white blood cell count and in serum cholesterol were found after GdAc at 0.18 mmol/kg cumulative dose. Analogously, gadolinium content in target organs (as % of injected dose) after any of contrast media was 100-200 times lower than after GdAc, either after single or repeated administrations. Under these experimental conditions, the rank of residual gadolinium found in these organs was GdAcOmniscan >Gadovist >MultiHance. Depopulation of lymphocytes in periarteriolar lymphatic sheaths (PALS) areas of the spleen was noted in rats treated with a single dose of GdAc sacrificed 24h post-dosing, but not in repeated dose rats sacrificed 48 h after last dosing. It was, therefore, concluded that this was a transient phenomenon and that PALS are rapidly repopulated with lymphocytes. With all contrast media, gadolinium content after a 2-day washout following a 3-week repeated administration period was lower than the amount found 24h after a single administration. Accordingly, the observed gadolinium content in organs should actually be in a complexed form (possibly the injected complex) which is subjected to elimination.

Animals↗

Computed model of gadolinium enhanced MRI of breast disease.

OBJECTIVE: Investigation has shown that the most useful MRI finding for the detection of breast cancer is enhancement following in travenous contrast. However, many widely different imaging protocols have been used. The purpose of this study is to explicate factors that affect the signal intensity of breast lesions after intravenous gadolinium. METHODS AND MATERIALS: A computer model was developed using equations based on published data. The effect of gadolinium on breast tissues was calculated using the model with appropriate values for baseline tissue relaxation times, relaxivity of gadolinium at the given field strength and concentration of gadolinium based on published data, for the TR, TE, flip angle and field strength of several published sequences used for enhanced breast MRI. RESULTS: The computer model allows comparison of the performance of different sequences, which can be displayed graphically. These vary in their performance, largely dependent on T1 weighting. Enhancement is also affected by the baseline of the T1 of the lesion and sensitivity of the sequence to gadolinium. Malignant lesions demonstrate greater observed enhancement than predicted when assuming symmetric distribution of contrast, indicating there is greater accumulation of gadolinium, accounting for the differential enhancement between benign and malignant lesions. CONCLUSIONS: MRI sequences vary greatly in their demonstration of enhancement after intravenous gadolinium contrast. Numerical diagnostic criteria such as % signal intensity change must be interpreted with care when using a different sequence than that on which the criterion was developed. There is preferentially greater accumulation of contrast in malignant lesions, whether due to angiogenesis or altered permeability.

Algorithms↗

Comparison of triple dose versus standard dose gadolinium-DTPA for detection of MRI enhancing lesions in patients with MS.

We studied whether a triple dose of gadolinium-DTPA alone or in combination with delayed scanning increases the sensitivity of brain MRI for detecting enhancing lesions in patients with MS. We obtained T1-weighted brain MRI scans in two sessions for 22 patients with clinically definite MS. In the first session, we obtained one scan 5 to 7 minutes after the injection of 0.1 mmol/kg gadolinium-DTPA (standard dose). In the second session, 6 to 24 hours later, we obtained one scan before the two scans 5 to 7 minutes (for all patients) and one hour (for 11 patients) after the injection of 0.3 mmol/kg gadolinium-DTPA (triple dose). We detected 83 enhancing lesions in 14 patients when the standard dose of gadolinium-DTPA was used. The numbers of enhancing lesions increased to 138 (average increase 66%; p = 0.001) and the numbers of patients with such lesions to 18 (increase 28%) when we used the triple dose of gadolinium-DTPA. In addition, the total area per patient occupied by such lesions was greater (p < 0.0001) and lesion signal intensity higher (p = 0.0001) on the triple-dose scans than the standard-dose scans. There was an increase in the number of large enhancing lesions (p = 0.03) in the scans obtained 1 hour after the injection of the triple dose of gadolinium-DTPA. These data indicate that in patients with MS, a triple dose of gadolinium-DTPA can reveal many more enhancing lesions, which also appear larger. This suggests that the pathologic nature of "active" lesions in MS is heterogeneous, which might have impact on planning clinical trials.

Contrast Media↗

Pyogenic hepatic abscesses: MRI findings on T1- and T2-weighted and serial gadolinium-enhanced gradient-echo images.

The purpose of this study was to determine the magnetic resonance imaging (MRI) features of pyogenic hepatic abscesses on T1-weighted, T2-weighted, and serial gadolinium (Gd)-enhanced T1-weighted spoiled gradient-echo (SGE) images including images acquired in the immediate, intermediate, and late phases of enhancement. The MRI studies of 20 patients with pyogenic liver abscesses were retrospectively reviewed. All patients were examined on 1.5 (n = 19) and 1.0 (n = 1) T MR scanners. MR studies included T1-weighted, T2-weighted, and serial Gd-enhanced SGE images. The following determinations were made: signal intensity of the abscess cavity and perilesional liver tissue, and the presence of internal septations, layering material, or air in the abscess cavity. The pattern of enhancement of the abscess wall, internal septae and peri-abscess liver were evaluated on serial Gd-enhanced SGE images. A total of 53 abscesses were observed in the 20 patients. Fortyeight abscesses were hypointense on T1-weighted and hyperintense on T2-weighted images. Internal septations were present in four abscesses. Lower signal intensity material was observed in a dependent location on T2-weighted images in one abscess. Signal void foci of air located on the nondependent surface was observed in two abscesses. Two other abscesses contained signal void air that occupied the entire abscess cavity, observed on all imaging sequences. On serial gadolinium-enhanced images, all abscesses revealed early enhancement of the wall, which persisted with negligible change in degree of enhancement or thickness on delayed images. Abscess walls ranged in thickness from 2 to 5 mm. Internal septations ranged in thickness from 2 to 3 mm. Abscess walls and septations were relatively uniform in thickness with no evidence of focal nodularity. Periabscess liver tissue was mildly hypointense on T1-weighted and mildly hyperintense on T2-weighted images in 20 lesions, which were either circumferential (n = 12) or wedge-shaped (n = 8). All these regions enhanced more than the remainder of the liver on immediate post-gadolinium images and remained relatively hyperintense on late phase images. Periabscess liver parenchyma was isointense on both T1- and T2-weighted images in 18 lesions, and in these lesions wedge-shaped subsegmental (n = 6) or segmental (n = 12) enhancement was observed on immediate gadolinium-enhanced images, which faded to isointensity on intermediate phase images. No perilesional signal changes and enhancement difference was observed in 15 lesions. Characteristic features of abscesses include: intense mural enhancement on early gadolinium-enhanced images, which persists with negligible change in thickness and intensity on later post-gadolinium images, and the presence of periabscess increased enhancement on immediate post-gadolinium images. These MRI features may help to distinguish abscesses from other focal liver lesions during differential diagnosis.

Contrast Media↗

Nephrotoxicity of high-dose gadolinium compared with iodinated contrast.

To determine if high-dose gadolinium chelates are less nephrotoxic than iodinated contrast. Records of 342 patients who had received high-dose gadolinium (.2 to .4 mmol/kg) for magnetic resonance imaging were reviewed to identify patients who had also received iodinated contrast for radiographic examinations. Their clinical course and laboratory data were reviewed to identify changes in serum creatinine attributable to the contrast agents. In 64 patients, serum creatinine data were available pre and post both gadolinium and iodinated contrast. The mean change in serum creatinine after gadolinium in these 64 patients was -.07 mg/dL (-6 mumol/L). By comparison, the mean change in serum creatinine in the same patients after iodinated contrast was .35 mg/dL (+31 mumol/L) from 2.0 +/- 1.4 to 2.3 +/- 1.8 (P = .002). Eleven of the 64 patients had iodinated contrast-induced renal failure (.5 mg/dL or greater rise in serum creatinine); none had gadolinium contrast-induced renal failure despite the high gadolinium dose and high prevalence of underlying renal insufficiency. High-dose gadolinium chelates are significantly less nephrotoxic than iodinated contrast.

Adolescent↗

Nodule-in-nodule appearance of hepatocellular carcinomas: comparison of gadolinium-enhanced and ferumoxides-enhanced magnetic resonance imaging.

PURPOSE: To perform comparison of gadolinium-enhanced and ferumoxides-enhanced magnetic resonance imaging (MRI) in the detection of nodule-in-nodule appearance of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: During a recent 45-month period, we had eight patients (five men and three women; age range, 63-84 years; mean, 71 years) with HCCs with nodule-in-nodule appearance who underwent gadolinium-enhanced MRI, ferumoxides-enhanced MRI, and computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), combined and separately, within an interval of two weeks. Two blinded radiologists in consensus retrospectively evaluated three sets of sequences: unenhanced T1- and T2-weighted MR, gadolinium-enhanced MR, and ferumoxides-enhanced MR images in random order of patients and imaging sequences. The depiction degree of nodule-in-nodule appearance of HCC was evaluated in a semiquantitative fashion. The sensitivities of unenhanced T1- and T2-weighted, gadolinium-enhanced, and ferumoxides-enhanced MR images were compared with McNemar's test. RESULTS: The eight HCCs with nodule-in-nodule appearance ranged in size from 16-26 mm (mean, 20.0 +/- 4.0 mm), and there existed nine internal HCC foci ranging in size from 5-14 mm (mean, 7.9 +/- 3.5 mm). On gadolinium-enhanced MR images, the nodule-in-nodule appearance of HCC was typically seen as hypervascular foci in an iso- or hypovascular area: the depiction degree of nodule-in-nodule appearance was distinct in two lesions, equivocal in three, and absent in three. On ferumoxides-enhanced MR images, it was typically seen as hyperintense foci in a hypointense area: the depiction degree was distinct in four, moderate in one, and absent in three. The sensitivities for detection of nodule-in-nodule appearance were 25%, 25%, and 63% on T1- and T2-weighted, gadolinium-enhanced, and ferumoxides-enhanced MR images, respectively, but there was no significant difference in sensitivity. CONCLUSION: Nodule-in-nodule appearance of HCCs can be seen on ferumoxides-enhanced MR images, in some cases more clearly than on gadolinium-enhanced MR images, particularly when the background nodule shows hyperintensity on precontrast T1-weighted images. Ferumoxides-enhanced MRI may be considered when development of malignant foci is suspected during routine examinations.

Aged↗

Detection of hepatocellular carcinoma by ferumoxides-enhanced MR imaging in cirrhosis: Incremental value of dynamic gadolinium-enhancement.

PURPOSE: To investigate the incremental value of dynamic gadolinium-enhancement performed immediately after ferumoxides-enhanced magnetic resonance (MR) imaging on the detection of hepatocellular carcinoma in patients with cirrhosis. MATERIALS AND METHODS: We retrospectively reviewed MR scans of 62 cirrhotic patients over a two-year period. Sequences included ferumoxides-enhanced T2-weighted fast spin echo followed by dynamic gadolinium-enhanced T1-weighted spoiled gradient echo. Two readers independently documented the presence of hepatocellular carcinoma on a three-point confidence scale, without and with gadolinium-enhanced images. The presence or absence of hepatocellular carcinoma was established by histopathology (58 patients) or follow-up imaging (four patients) over a mean period of nine months. RESULTS: A total of 71 hepatocellular carcinomas were found in 42 patients. There was no statistically significant difference in sensitivity for the diagnosis of hepatocellular carcinoma without vs. with gadolinium-enhanced images (68% vs. 74% for reader 1 and 62% vs. 73% for reader 2, respectively, P > 1.3). However, both readers showed a lower mean confidence for tumor detection without vs. with gadolinium-enhanced images (2.3 vs. 2.7 for reader 1, 2.3 vs. 2.9 for reader 2, P < 0.01). CONCLUSION: In our study, the addition of dynamic gadolinium-enhancement to ferumoxides-enhanced MR imaging did not improve hepatocellular carcinoma detection, but the addition of gadolinium-enhancement is recommended if ferumoxides-enhanced imaging is used because it increased reader confidence.

Adolescent↗

The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

OBJECTIVES: We sought to identify the histologic basis of myocardial late gadolinium enhancement cardiovascular magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM). BACKGROUND: The histologic basis of late gadolinium CMR in patients with HCM is unknown. METHODS: A 28-year-old male patient with HCM and heart failure underwent late gadolinium enhancement CMR and, 49 days later, heart transplantation. The explanted heart was examined histologically for the extent of collagen and disarray, and the results were compared with a previous in vivo CMR scan. RESULTS: Overall, 19% of the myocardium was collagen, but the amount per segment varied widely (SD +/- 19, range 0% to 71%). Both disarray and collagen were more likely to be found in the mesocardium than in the endo- or epicardium. There was a significant relationship between the extent of late gadolinium enhancement and collagen (r = 0.7, p < 0.0001) but not myocardial disarray (p = 0.58). Segments containing >15% collagen were more likely to have late gadolinium enhancement. Regional wall motion was inversely related to the extent of myocardial collagen and late gadolinium enhancement but not disarray (p = 0.0003, 0.04, and NS, respectively). CONCLUSIONS: In this patient with HCM and heart failure, regions of myocardial late gadolinium enhancement by CMR represented regions of increased myocardial collagen but not disarray.

Adult↗

"Bull's-eye" sign on gadolinium-enhanced magnetic resonance venography determines thrombus presence and age: a preliminary study.

PURPOSE: Venous thrombosis is associated with a significant inflammatory response, which can be visualized by gadolinium magnetic resonance venography (MRV). Gadolinium extravasates into tissue during inflammation, producing perithrombus enhancement on magnetic resonance scanning. This study determines (1) whether gadolinium enhancement occurs during deep venous thrombosis (DVT); and (2) whether this enhancement changes with time and can therefore establish the age of thrombus. METHODS: Patients with a diagnosis of iliofemoral DVT by duplex ultrasound who were referred for MRV to document central thrombus extent were studied. T1 weighted images were obtained before and after gadolinium injection (0.1 mmol/kg); repeat scans were obtained up to 3 months thereafter. At the level of maximum thrombus, measurements of signal intensity were made at the periphery (rim), and the center of the thrombosed vein, as well as the contralateral normal vein, on images after gadolinium enhancement. Rim-center vein signal intensity ratios were then calculated and followed. RESULTS: A total of 39 scans were obtained in 14 patients (eight men, six women). The thrombosed veins were enlarged, with a peripheral rim of enhancement ("bull's-eye" sign). The rim-center ratio for thrombosed veins (2.16 +/- 0.18) was different from that of normal veins (0.66 +/- 0.10; n = 39; p < 0.001). For all acute studies (< or = 14 days) the rim-center ratio was 2.38 +/- 0.17 (n = 31), whereas for all chronic studies (> 14 days) the rim-center ratio was 1.29 +/- 0.44 (n = 8; p = 0.001). Among patients who underwent both early and late studies, the rim-center ratio dropped significantly, from 2.33 +/- 0.20 acutely to 1.29 +/- 0.44 in chronic studies (n = 8; p = 0.03). One patient with active malignancy had a paradoxic increase in rim-center ratio over time and a clinical recurrence of symptoms, suggesting active thrombosis. CONCLUSIONS: We conclude that (1) a pattern of peripheral gadolinium enhancement (bull's-eye sign) is seen around acutely thrombosed veins on gadolinium-enhanced MRV, facilitating DVT diagnosis; and (2) the ratio of signal intensity at the rim versus the center of the thrombosed vein may be a good discriminator of acute compared with chronic DVT, which may help direct therapy.

Acute Disease↗

Gadolinium as a nonnephrotoxic contrast agent for catheter-based arteriographic evaluation of renal arteries in patients with azotemia.

OBJECTIVE: This study was undertaken to determine the effect of gadolinium arteriography on renal function and its diagnostic accuracy in patients with azotemia with suspected renovascular disease. METHODS: Catheter-based digital subtraction arteriographic studies with gadolinium as the contrast agent were performed on 25 occasions in 21 consecutive patients with azotemia to evaluate renal arterial circulation. Gadolinium (gadodiamide, 287 mg/mL) was the only contrast used in these studies. Quantities of gadolinium administered ranged from 40 to 264 mL (mean +/- standard deviation, 124 +/- 74 mL). Serial determinations of renal function were performed in all patients. Arteriography was undertaken 20 times after prior renal revascularizations: seven times as a routine postoperative follow-up study, nine for increasing azotemia, three for worsening hypertension, and once for evaluation of a known renal artery stenosis in patient with an abdominal aortic aneurysm. Three additional arteriograms were performed as part of an evaluation for suspected renovascular hypertension. The two remaining arteriograms were performed in patients with known aortic aneurysms in whom renal artery stenosis was suspected. RESULTS: No adverse changes in renal function followed gadolinium arteriography. Prearteriography serum creatinine values ranged from 1.6 to 9.1 mg/dL (3.0 +/- 1.4 mg/dL), compared with postangiography values that ranged from 1.2 to 8.4 mg/dL (2.9 +/- 1.3 mg/dL). Comparable blood urea nitrogen values ranged from 23 to 71 mg/dL (40.1 +/- 13.5 mg/dL) before arteriography and from 21 to 68 mg/dL (36.5 +/- 13.3 mg/dL) after arteriography. All 38 renal arteries evaluated were adequately imaged. First-order and second-order branchings were well visualized on selective renal studies. Twenty-one renal arteries showed no abnormalities, including six of seven reconstructed arteries subjected to early postoperative evaluation. Twelve renal arteries manifested significant disease, including seven with stenoses and five that had become occluded. Among five additional renal arteries studied, two exhibited obstructing thrombus, two had dissections, and one had a kinked aortorenal bypass graft. CONCLUSION: Catheter-based arteriography in patients with azotemia with gadolinium as a contrast agent is a safe and effective means to evaluate the renal arterial circulation. The preferential use of gadolinium in lieu of nephrotoxic iodinated contrast agents for catheter-based arteriography in patients with azotemia is supported by this experience.

Adult↗

The safety of gadolinium in patients with stage 3 and 4 renal failure.

BACKGROUND: Although there is a well-documented risk of acute renal failure (ARF) with the iodinated contrast agents, intravenous gadolinium-based contrast agents are considered non-nephrotoxic and have been widely used for magnetic resonance imaging (MRI). However, debate continues regarding the safety issue of gadolinium, especially in patients with kidney failure. Therefore, we aimed to evaluate the safety of gadolinium in patients with stage 3 and 4 renal failure as well as risk factors for nephrotoxicity. METHOD: We retrospectively analysed 473 patients with chronic renal failure who underwent angiographic MRI procedures in our centre from February 1999 to March 2005 in whom gadolinium was used as the sole contrast agent at a dose of 0.2 ml/kg. Among them, 91 patients with stage 3 or 4 renal failure according to K/DOQI definition, who had available data in their files, were enrolled in the study. The ARF was defined as an increase of at least 0.5 mg/dl in serum creatinine level over baseline after using gadolinium. RESULTS: Eleven of 91 (52 males, 39 females; median age 59 years; median estimated glomerular filtration rate (eGFR) 33 ml/min/1.73 m2) patients developed ARF (12.1%). The median eGFR was lower in patients with ARF than in those who did not develop ARF. The risk factors for ARF were baseline eGFR, older age, diabetic nephropathy and low baseline haemoglobin and albumin levels. Baseline eGFR and diabetic nephropathy were determined as the independent risk factors in regression analysis. CONCLUSIONS: An ARF can occur after gadolinium-based contrast agents in patients with moderate to severe chronic renal failure. Risk factors for ARF after gadolinium toxicity include diabetic nephropathy and low GFR.

Acute Kidney Injury↗

The use of gadolinium chelates for X-ray digital subtraction angiography.

RATIONALE AND OBJECTIVES: To evaluate the feasibility and safety of using gadolinium chelates for x-ray digital subtraction angiography (DSA) in patients with contraindications to iodinated contrast material. METHODS: We performed 30 DSAs in 22 patients (5 females, 17 males; mean age 64.9 years) with contraindications to iodinated contrast media (renal insufficiency: n = 28; hyperthyroidism: n = 1; contrast allergy: n = 2). Gadolinium chelates were administered as 0.5 mol/L solutions (mean volume of gadolinium chelates per patient was 34 +/- 19 mL). Gadolinium chelates were the sole contrast agent in 17 examinations, were used in conjunction with carbon dioxide (CO2) in 8 studies, (mean 212 +/- 226 mL), and were combined with the restricted use of nonionic iodinated contrast (mean 12.8 +/- 4.7 mL) in 6 examinations. We carried out 15 diagnostic angiographies and 15 percutaneous transluminal angioplasties. RESULTS: Use of gadolinium chelates allowed us to obtain diagnostic angiographic images in all cases. However, the quality of angiograms was inferior compared with that obtained with iodinated contrast agents and superior compared with CO2 as the contrast material. Adverse events were not noted. Mean serum creatinine was 2.6 +/- 1.5 mg/dL before and 2.3 +/- 1.0 mg/dL after DSA. No patient developed contrast-induced nephropathy. CONCLUSIONS: Gadolinium chelates produce an x-ray DSA intermediate in image quality between iodinated contrast and CO2. Digital subtraction angiography with intra-arterial gadolinium chelate administration may offer an alternative to iodinated contrast material in patients with contraindications to iodine.

Aged↗

Motexafin gadolinium: a redox-active tumor selective agent for the treatment of cancer.

PURPOSE OF REVIEW: Redox regulation has been shown to be an important component of malignant cell survival and is a system that may be pharmacologically manipulated for the treatment of cancer. Motexafin gadolinium is a member of a class of rationally designed porphyrin-like molecules called texaphyrins. The rationale for its use in cancer therapy is that, like naturally occurring porphyrins, it tends to concentrate selectively in cancer cells and it has a novel mechanism of action as it induces redox stress, triggering apoptosis in a broad range of cancers. RECENT FINDINGS: In vitro studies have shown that motexafin gadolinium is synergistic with radiation and varied chemotherapeutic agents. A phase III international study has shown that the onset of neurologic progression is significantly delayed in patients with brain metastases from lung cancer treated with whole-brain radiation and motexafin gadolinium (compared with radiation alone). Recent preclinical data have shown that motexafin gadolinium alone is cytotoxic to cancers such as multiple myeloma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia through redox and apoptotic pathways. Multiple clinical trials examining motexafin gadolinium as a single agent and in combination with radiation and/or chemotherapy for the treatment of solid and hematopoietic tumors are underway. SUMMARY: Motexafin gadolinium is a novel tumor-targeted agent that disrupts redox balance in cancer cells by futile redox cycling. Motexafin gadolinium is currently in numerous hematology/oncology clinical trials for use as a single agent and in combination with chemotherapy and/or radiation therapy.

Antineoplastic Agents↗