Contrast-enhanced MR imaging of the breast: comparison of two different doses of gadopentetate dimeglumine.

PURPOSE: To optimize detection and diagnosis of breast lesions with contrast-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: A three-dimensional fast low-angle shot pulse sequence was used for a group comparison consisting of 76 high-dose (0.16 mmol gadopentetate dimeglumine per kilogram of body weight) and 76 low-dose (0.1 mmol/kg) examinations. Intraindividual comparisons were possible in a subgroup of 20 patients. RESULTS: Enhancement with the high dose was about 1.5 times higher for benign and malignant tissues. With the lower dose, no false-positive findings could be avoided and definition of a threshold that excluded false-negative findings was problematic. Conspicuity of malignant lesions was much improved with the higher dose (a good to excellent rating in 81% vs 26% with the lower dose). Three small foci were visible only with the higher dose. CONCLUSION: The higher dose of contrast material allowed much better results. Dose comparison studies are also recommended for other techniques.

Triple-dose versus standard-dose gadopentetate dimeglumine: a randomized study in 199 patients.

To investigate the safety, patient tolerance, and efficacy with 0.3 mmol/kg gadopentetate dimeglumine in magnetic resonance (MR) imaging of the central nervous system (CNS), a phase 3 trial was conducted in 199 patients with suspected CNS lesions. Patients received either 0.1 or 0.3 mmol/kg gadopentate dimeglumine (injection time, 15 seconds and 45 seconds, respectively). T1- and T2-weighted spin-echo sequences were performed at either 0.5 T or 1.5 T. In 80 patients with enhancing brain lesions, contrast-to-noise ratios (C/Ns) were calculated, and lesion-to-brain contrast was evaluated visually. Six patients (6%) in each dose group reported adverse events. Eight adverse events occurred with 0.1 mmol/kg and seven with 0.3 mmol/kg. Vital signs and laboratory values did not change significantly. C/N (P < .05) and visual assessment ratings were higher with 0.3 mmol/kg than with 0.1 mmol/kg. According to these preliminary results, 0.3 mmol/kg gadopentetate dimeglumine is safe and well tolerated when administered at approximately 1 mL/sec.

[The regional blood flow in intracranial tumors: a comparison of HMPAO-SPECT with a newer magnetic resonance tomographic procedure]. / Regionale Durchblutung bei intrakraniellen Tumoren: Vergleich der HMPAO-SPECT mit einem neueren magnetresonanztomographischen Verfahren.

We compared the value of gadolinium-enhanced first-pass MRI perfusion studies and HMPAO-SPECT for the assessment of regional cerebral blood flow in a prospective study of 23 intracranial tumour patients. In five tumours with homogeneous hypoperfusion and eight tumours with homogeneous hyperperfusion, tumour blood flow patterns in MRI and HMPAO-SPECT were similar. By contrast, in ten patients with inhomogeneous tumour blood flow pattern only MRI was able to differentiate between tumour areas with no or low flow, tumour tissue with high flow, and perifocal oedema with reduced flow. In HMPAO-SPECT, these inhomogeneous tumours were represented as areas of homogeneously reduced tracer retention corresponding to different tumour constituents and perifocal oedema. In conclusion, the high spatial resolution of MRI enables a detailed analysis of tumour blood flow.

Administration of gadopentetate dimeglumine in MR imaging of intracranial tumors: dosage and field strength.

PURPOSE: To investigate the efficacy of 0.025, 0.05 and 0.1 mmol/kg gadopentetate dimeglumine in MR imaging of patients with intracranial tumors at mid and high field strength. METHODS: In 88 patients, an open-label phase III multicenter dose-finding study was performed at 0.5, 1.0, and 1.5 T MR units. Before and after (5, 15, 25 minutes) intravenous administration of gadopentetate dimeglumine, imaging was performed with T1-weighted spin-echo sequences. RESULTS: With 0.1 mmol/kg yielding the highest values, tumor enhancement and numerical tumor/brain contrast showed dose-dependent 5-minute postcontrast values (P less than 0.05). Compared to 5-minute postcontrast values, there was no significant change at 15 and 25 minutes. Although the lowest values of enhancement were found at 0.5 T, differences in enhancement among the field strengths were not statistically significant. The numerical data were confirmed by visual assessment of tumor/brain contrast. Eighty to 90% of cases had diagnostically valuable enhancement at 0.1 mmol/kg, 50% at 0.05 mmol/kg, and 10% at 0.025 mmol/kg (P less than 0.05). There were no adverse events. CONCLUSION: Our results confirm that 0.1 mmol/kg gadopentetate dimeglumine is more effective at enhancing intracranial tumors than lower doses at mid and high field MR units.

[Pharmacokinetics of gadolinium-DTPA in chronic renal insufficiency requiring dialysis]. / Pharmakokinetik von Gadolinium-DTPA bei dialysepflichtiger chronischer Niereninsuffizienz.

MRT with gadolinium-DTPA (0.1 mmol/kg body weight) was performed in 10 patients with renal insufficiency requiring dialysis and the clearance of gadolinium-DTPA was studied. After 3 dialysis on 3 successive days more than 97% of the initial concentration of gadolinium-DTPA had been eliminated. Average half-life was 1.87 hours. There were no side effects in any of the patients. Close laboratory observation of liver function showed no significant changes during the period of study. No contra-indication for the use of this contrast medium in patients with renal insufficiency requiring dialysis was found during this study.

[The regional cerebral circulation in infarct patients. Rapid dynamic T2*-weighted MRT after a bolus injection of gadolinium-DTPA]. / Regionale Gehirndurchblutung bei Infarktpatienten. Schnelle dynamische T2*-gewichtete MRT nach Gadolinium-DTPA-Bolusinjektion.

The aim was to validate the MRI assessment of regional cerebral blood flow. Measurements were performed on a 1.5 T imaging system using a fast T2*-weighted gradient-echo sequence. After intravenous injection of gadolinium-DTPA 30 images were acquired in the same slice position during 84 seconds. In 12 volunteers we observed a symmetrical cortical decrease of signal intensity during the passage of the contrast medium. In 9/23 patients with impairment of cerebral blood flow a circumscribed area of reduced signal intensity decrease (hypoperfusion) was found. In 4/23 patients the decrease of signal intensity was more pronounced than in normals (hyperfusion). In 9/23 patients signal intensity changes were normal. HMPAO-SPECT confirmed successful MRI assessment of cerebral blood flow in 22/23 patients.

Renal tolerance of gadolinium-DTPA/dimeglumine in patients with chronic renal failure.

Safety data for renal tolerance of gadolinium-DTPA(Gd-DTPA)/dimeglumine were evaluated in 21 patients (age: mean +/- standard deviation [SD], 58 +/- 12 years) with impaired renal function. The mean +/- SD serum creatinine level at baseline was 213 +/- 101 mumol/L (range, 89.2-551 mumol/L). Creatinine clearance at baseline averaged 34.5 +/- 19.2 mL/minute (range, 7.2-70 mL/minute). Gd-DTPA was injected at a dose of 0.1 mmol/kg body weight. Serum parameters (creatinine, sodium, and potassium) were determined before and 6, 24, 48, and 120 hours after administration of Gd-DTPA. Urinary parameters (N-acetyl-beta-D-glucosaminidase [beta-NAG], protein, and albumin) were determined before (spot urine sample) and after treatment for collection periods 0 to 3, 3 to 6, 6 to 12, 12 to 24, and 24 to 48 hours. A final spot urine sample was taken at 120 hours. There was no significant statistical change of serum creatinine level within the observation period, and there was no single patient matching the criteria of acute renal failure (increase of serum creatinine level of 88.4 mumol/L [1 mg/dL] or more within 48 hours after injection). Serum values of sodium and potassium levels remained unchanged. Beta-NAG was slightly increased 0 to 3 hours after injection, but returned to baseline values during the collection periods up to 120 hours. There was no increase of protein or albumin excretion. These preliminary results suggest Gd-DTPA has good renal tolerance in patients with pre-existing chronic renal failure.

Dermoid cyst with crystalline inclusions in adjacent cortex: an ultrastructural study.

Dermoids are rare tumors of the central nervous system. So far, no electron microscopic studies of these tumors have been available. We describe the histology and ultrastructure of a dermoid cyst in a patient with situs inversus and discuss the relationship of keratin and aseptic meningitis, a well-known complication. Histological examination showed an epidermal matrix with 2-4 layers, a cyst containing keratin and debris, some hairs and sebaceous glands. In some areas, chronic inflammation had destroyed the matrix of the cyst wall. Gliosis of the adjacent brain parenchyma was evident, as were eosinophilic rod-shaped crystals. Electron microscopy revealed gliosis with Rosenthal fibers in brain parenchyma adjacent to the tumor capsule. Intracellular osmiophilic, crystalline inclusions were prominent within this area. Glial cells and neuropil were spared. No gross intracellular pathology was seen.

Therapy with male pathological gamblers: Between self help group and group therapy-Report of a developmental process.

A therapy project was developed for pathological gambling patients and, within a three year period, more than 60 gamblers were studied and treated. Diagnostic evaluation was made according to DSM-III. In addition to individual and family therapy, we designed a voluntary group setting. In this report, we concentrate first on the development of group work, then on some psychodynamic hypotheses about the personality of the gambler. We also try to show the correspondence between these hypotheses and the group process. Pathological gambling is seen as an attempt at self-healing and a strategy of conflict-solving; the slot machine, as an inanimate object, offers a temporary symbiosis with clear limitations; the gambling will come to a guaranteed end, either when all of the money is lost, or when gaming ends at night. Finally, we list some recommendations for the treatment of gamblers in group therapy.

Safety of gadolinium-DTPA: extended clinical experience.

This review reports data on the general and renal tolerance of the paramagnetic contrast agent Gd-DTPA after intravenous administration. Gd-DTPA was administered usually at a dose level of 0.1-0.2 mmol/kg body wt (range: 0.005-0.25 mmol/kg body wt) in cranial, spinal and body MR indications. In phase I-IIIa studies a total of 2154 healthy volunteers and patients were investigated, usually at a dose of 0.1 mmol/kg body wt. From the obtained results it was concluded that adverse events (AEs) may be expected in the order of magnitude of 1%. In phase IIIb-IV studies 13,439 patients were investigated at 0.1 or 0.2 mmol/kg body wt. Tolerance data were collected according to a standardized protocol and metaanalysis of obtained data was performed. AEs, irrespective of their drug relationship, were observed in 1.15% of the patients. The observed AEs were comparable to those after intravenous administration of iodinated nonionic X-ray contrast media. There was no correlation between patient age and the incidence of AEs. In patients with a known history of allergy the incidence of AEs increased to 2.6%. In pediatric use no added risk was observed in a total of 826 neonates, children, and adolescents up to 18 years of age. Gd-DTPA showed good renal tolerance in patients with and without preexisting impairment of renal function. A prospective open safety and pharmacokinetic study was conducted in patients with hemodialysis. Gd-DTPA was shown to be eliminated completely by hemodialysis. Fast bolus injections were tolerated without added risk. Presented data from postmarketing surveillance (up to March 31, 1991) cover an estimated total of more than 2,000,000 applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Tolerance data of Gd-DTPA: a review.

Gd-DTPA is the first paramagnetic contrast agent approved for clinical use in cranial and spinal MRI in the F.R.G., U.S.A., Japan and several other countries. After submission 13,439 patients were enrolled in standardized protocolled clinical trials. The observed adverse drug reactions (ADRs) after i.v. injection of Gd-DTPA were comparable to those after administration of iodinated non-ionic roentgen contrast media (CM). However, the overall incidence of ADRs after intravenous injection of 0.1 or 0.2 mmol/kg body weight Gd-DTPA was found to be even lower. Adverse events were observed in only 1.46% of the patients - or 1.14% if localized warmth is excluded. None of them was critical. There was no correlation between patient age and the incidence of ADRs. In patients with a known history of allergy the incidence of ADRs was increased by a factor 3-4, which is still lower than the incidence reported after intravenous administration of iodinated non-ionic roentgen CM to patients without known allergy. Good renal tolerance was seen in all patients, irrespective of pre-existing renal impairment. Fast bolus injections of Gd-DTPA were tolerated without added risk. The favorable safety profile is also reflected in the post marketing surveillance reports since Gd-DTPA became available as a commercial drug.

Elimination of Gd-DTPA by means of hemodialysis.

After intravenous administration of Gd-DTPA (0.1 mmol/kg) hemodialysis was performed five times within 6 days in a patient with endstage renal failure. During the fifth hemodialysis a blood sample of 5 ml was withdrawn and Gd-concentration was measured in plasma at 342.247 nm using the method of Inductively Coupled Plasma Atomic Emission Spectrometry. Gd-concentration measured in venous and arterial blood was 6 x 10(-6) mol/liter, corresponding to 1.5% of the dose administered. If these data can be confirmed in more patients with endstage renal failure, this is the proof of effective hemodialysis of Gd-DTPA in a clinical setting.

[Optimization of gadolinium-DTPA dose: an inter-individual study of patients with intracranial tumors]. / Dosisoptimierung von Gadolinium-DTPA: Eine interindividuelle Studie an Patienten mit intrakraniellen Tumoren.

The diagnostic value of various doses of Gd-DTPA was compared intra-individually. Thirty-three patients with cerebral tumours were randomly allocated to three groups. Group 1 was given a dose of 0.025, group 2 a dose of 0.05 and group 3 a dose of 0.1 mmol GD-DTPA/kg body weight. Following administration of Gd-DTPA the average tumor/brain contrast in group 1 was -4.5%, in group 2 +8.4% and in group 3 +43.0%. Diagnostically useful tumour delineation was obtained in two out of 11 in group 1, in seven out of 11 in group 2 and in 10 out of 11 in group 3. A further increase in the dose to 0.2 mmol/kg body weight in group 3 resulted in a further increase in tumour/brain contrast of +62.5% and improved tumour delineation in one case. As a result of these findings a dose of 0.1 mmol Gd-DTPA/kg body weight is recommended for the routine investigation of intracranial tumours.

Comparison of plain and Gd-DTPA-enhanced MR-imaging in children.

40 children and adolescents (aged 1-16 years) were examined by MRI at 1.0 T. Gd-DTPA was given intravenously at a dose of 0.1 mmol/kg body weight. In all cases T1-weighted SE sequences were used to demonstrate contrast enhancement. No adverse effects were seen. 30 patients had one or more lesions; in 20 patients contrast enhancement was seen. In 4 cases lesions were not observed by plain MRI and could only be detected after Gd-DTPA. In addition, contrast enhancement provided additional information about the differentiation of lesion from edema or necrosis in 13 patients. Normal brain matter did not show any changes in signal intensity. However, an age-dependent signal increase was found in the normal vertebral bone marrow in all children. Gd-DTPA should be used as a supplementary examination whenever a tumor or an infectious disease of the CNS is suspected and plain MRI is normal, or when origin and extent of a lesion cannot be adequately defined with plain MRI.

The Werner syndrome: a case study.

We present the neuropathological data of a 49-year-old patient with a history of Werner syndrome: The main features were arteriosclerosis of the small intracerebral arteries, cerebral atrophy and vascular myelopathy. In addition, there were marked lipofuscin deposition and corpora amylacea, but no neurofibrillary tangles or plaques. In comparison with pathological findings in other organ systems, the central nervous system shows mainly degenerative pathology in this disease.

[Homologous cerebral atrophy and ischemic insults in progeria adultorum]. / Homologe zerebrale Atrophie und ischämische Insulte bei Progeria adultorum.

Neuropathological findings obtained from a female patient, 49 years of age, with progeria adultorum (Werner's syndrome) are described in this paper. Vascular sclerosis with multiple ischaemic infarctions, cerebral atrophy, and vascular myelopathy were the most strongly pronounced CNS findings. Also recorded were severe lipofuscin depositions from the cortex, dentate nucleus, and olivae as well as amylaceous bodies in the insula of Reil and the hippocampus. Neurofibrillary tangles or plaques were not recordable. The central nervous system proved somewhat comparable to other organs, in that mesenchymal regressive changes were the main features.

Histologic characterization of 41 ependymomas with the help of a personal computer.

Fourty-one ependymomas were histologically analyzed in relation to patient age and sex and tumor location. A discriminant analysis model using Bayes' formula and a personal computer were employed. Ependymomas situated in the posterior fossa had a higher incidence in children. Ependymoblastomas were all situated above the tentorium and occurred only in young children. We identified three tumor groups on the basis of common histologic characteristics: benign ependymomas, anaplastic ependymomas, and ependymoblastomas. The main features useful for the grouping were the degree of differentiation and anaplasia. Ependymomas from the cauda equina showed histologic characteristics that allowed them to be differentiated from other benign ependymomas. In each group the particular histologic characteristics, age, and location were significant in terms of diagnosis and prognosis. This method of analysis may help to more precisely define ependymomas and may provide pathologists and clinicians with a quantifiable diagnostic tool that may be of help in establishing the appropriate treatment.

On the ultrastructure of ependymomas--a semiquantitative analysis of diagnostic criteria in 21 cases with special reference to glycogen as a marker.

We report our results on the ultrastructure of 21 ependymomas and establish the following diagnostic criteria: 1. Glycogen is the most frequently encountered criterion, followed by desmosomes, cilia, basal bodies and microvilli. Fifteen tumors had 3 or more of these features. 2. The allegedly typical nuclear pattern was found in only 6 cases. 3. Special ultrastructural features seen include basement membranes in a mid-thoracic ependymoma. Furthermore we propose the hypothesis that glycogen might be involved in cilia assembly.