Does higher gadolinium concentration play a role in the morphologic assessment of brain tumors? Results of a multicenter intraindividual crossover comparison of gadobutrol versus gadobenate dimeglumine (the MERIT Study).

BACKGROUND AND PURPOSE: Gadobenate dimeglumine has proved advantageous compared with other gadolinium-based contrast agents for contrast-enhanced brain MR imaging. Gadobutrol is a more highly concentrated agent (1.0 mol/L). This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative evaluation of brain tumors. MATERIALS AND METHODS: Adult patients with suspected or known brain tumors underwent 2 identical MR imaging examinations at 1.5T, 1 with gadobenate dimeglumine and the other with gadobutrol, both at a dose of 0.1-mmol/kg body weight. The agents were injected in randomized order separated by 3-14 days. Imaging sequences and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, global preference) and quantitatively for CNR and LBR. RESULTS: One hundred fourteen of 123 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumors, metastases, extra-axial tumors, "other" tumors, and "nontumor" (49, 46, 8, 7, and 4 subjects, respectively). Readers 1, 2, and 3 demonstrated preference for gadobenate dimeglumine in 46 (40.7%), 54 (47.4%), and 49 (43.0%) patients, respectively, compared with 6, 7, and 7 patients for gadobutrol (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all other qualitative end points. Inter-reader agreement was good for all evaluations (κ = 0.414-0.629). Significantly superior CNR and LBR were determined for gadobenate dimeglumine (P < .019, all readers). CONCLUSIONS: Significantly greater morphologic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadobutrol at an equivalent dose.

Diagnosis of CADASIL disease in normotensive and non-diabetics with lacunar infarct.

BACKGROUND: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is characterized by recurrent cerebral ischemic episodes of the lacunar subtype usually without traditional vascular risk factors. We investigated the frequency of CADASIL among selected patients with cerebral ischemia of the lacunar subtype. METHODS: we studied patients under 65 years old who presented cerebral ischemia of the lacunar subtype without hypertension, diabetes mellitus or other causes that explained the cerebral ischemia. On the skin biopsies, we performed immunostaining analysis on 5µm frozen sections with monoclonal antibody anti-Notch 3 (1E4). We also performed a genetic analysis of the Notch 3 gene (exons 3,4,5,6,11 and 19). RESULTS: of 1.519 patients analyzed, only 57 (3.7%) fulfilled the selection criteria, and 30 of them accepted to participated in the study. We studied 30 patients, mean age was 53 years (range 34 to 65), 50% were men and all patients suffered a lacunar stroke. Immunostaining analysis was positive in two patients (6.6%) and the genetic analysis confirmed a mutation characteristic of CADASIL in exon 4 nt 622C/T (Arg 182 Cys) and 694 T/C (Cys206Arg) respectively. CONCLUSIONS: CADASIL disease was present in 6.6% of patients younger than 65 years with a lacunar stroke and without hypertension or diabetes mellitus. Screening for CADASIL should be considered in these patients.

Contrast-enhanced MR imaging of brain lesions: a large-scale intraindividual crossover comparison of gadobenate dimeglumine versus gadodiamide.

BACKGROUND AND PURPOSE: The higher relaxivity of gadobenate dimeglumine compared with gadodiamide is potentially advantageous for contrast-enhanced brain MR imaging. This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative lesion enhancement. MATERIALS AND METHODS: Adult patients with suggested or known brain lesions underwent 2 identical MR imaging examinations at 1.5T, one with gadobenate dimeglumine and the other with gadodiamide. The agents were administered in randomized order separated by 3-14 days. Imaging sequences and postinjection acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, and global preference) and quantitatively for contrast-to-noise ratio (CNR). RESULTS: One hundred thirteen of 138 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumor, metastasis, extra-axial tumor, or other (47, 27, 18, and 21 subjects, respectively). Readers 1, 2, and 3 demonstrated global preference for gadobenate dimeglumine in 63 (55.8%), 77 (68.1%), and 73 (64.6%) patients, respectively, compared with 3, 2, and 3 patients for gadodiamide (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all qualitative end points and for CNR (increases of 23.3%-34.7% and 42.4%-48.9% [spin-echo and gradient-refocused echo sequences, respectively] for gadobenate dimeglumine compared with gadodiamide). Inter-reader agreement was good for all evaluations (kappa = 0.47-0.69). Significant preference for gadobenate dimeglumine was demonstrated for all lesion subgroup analyses. CONCLUSION: Significantly greater diagnostic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadodiamide at an equivalent dose.

Imaging of parasellar lesions.

UNLABELLED: The sellar and parasellar region is an anatomically complex area that represents a crucial crossroad of important adjacent structures, e.g. orbits, cavernous sinus and its content, polygon of Willis, hypothalamus through the pituitary stalk and dural reflections forming the diaphragm sellae and the walls of the cavernous sinuses. Although the cavernous sinus represents the most relevant parasellar structure, from the practical and clinical point of view all the structures that surround the sella turcica can be included in the parasellar region. CT and, mainly, MRI are the imaging modalities to study and characterise the normal anatomy and the majority of processes in this region. We present a practical short review of the most relevant CT and MRI characteristics, such as location, nature of contrast enhancement and presence of cystic components, together with clinical findings, which permit differentiation of the most frequent and less common lesions found in the parasellar region. LEARNING OBJECTIVES: -A short review of the anatomy and clinical symptoms related to the parasellar region. -Radiological characterisation, mainly by MRI, of the many lesions that alter the structure and function of sellar and parasellar anatomy. -Description of the MRI features that permit differentiation among less common lesions.

Magnetic resonance imaging of metastatic disease to the brain with gadobenate dimeglumine.

Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.

Gadobenate dimeglumine-enhanced magnetic resonance imaging of intracranial metastases: effect of dose on lesion detection and delineation.

Seventy-four patients with one to eight proven intraaxial metastatic lesions to the brain received a total gadobenate dimeglumine dose of 0.3 mmol/kg of body weight, administered as three sequential bolus injections of 0.1 mmol/kg, at 10-minute intervals over a 20-minute period. Quantitative and qualitative assessments of efficacy were performed after each injection and a full evaluation of safety was conducted. Cumulative dosing produced significant (P < 0.01) dose-related increases in lesion-to-brain (L/B) ratio and lesion signal intensity (SI) enhancement. Two independent, blinded assessors noted additional lesions, compared to unenhanced images in 31% and 33%, 49% and 42%, and 50% and 48% of patients after each cumulative dose, respectively. Significantly more lesions were noted after the first injection, compared to unenhanced images (P = 0.002 and P < 0.001; assessors 1 and 2, respectively), and after a second injection, compared to the first (P < 0.001 and P = 0.039; assessors 1 and 2, respectively). Neither assessor noted significantly more lesions after the third injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted by assessors 1 and 2 for 27% and 26%, 48% and 35%, and 42% and 41% of patients, respectively, following each injection. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced magnetic resonance imaging (MRI). For patients with one lesion observed after 0.1 mmol/kg of gadobenate dimeglumine, additional lesions were noted for 24% and 17% of patients (assessors 1 and 2, respectively) following a second 0.1 mmol/kg injection. Only assessor 2 noted additional lesions following the third 0.1 mmol/kg injection. The findings of on-site investigators concurred with those of the two off-site assessors. No safety concerns were apparent.

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.

MRI findings in Möbius syndrome: correlation with clinical features.

The authors studied the MRI findings of three patients with Möbius syndrome. Möbius syndrome is a rare congenital disorder characterized by complete or partial facial diplegia accompanied by other cranial nerve palsies. MRI demonstrated brainstem hypoplasia with straightening of the fourth ventricle floor, indicating an absence of the facial colliculus. These MRI features suggest the diagnosis of Möbius syndrome and correlate with the clinical and neurophysiologic findings.

MultiHance in the assessment of intracranial tumors: results of phase II clinical studies.

PURPOSE: To assess preliminarily the efficacy of 0.1 and 0.2 mmol/kg doses of MultiHance for contrast-enhanced magnetic resonance imaging of brain tumors. METHODS: Patients were imaged pre-dose using proton density (PD), T2-weighted and T1-weighted spin-echo sequences, and post-dose by repetition of the T1-weighted sequences at 0-15, 15-30, 30-45 and 45-60 min after the completion of MultiHance administration. Qualitative efficacy assessments of the image sets were performed by two blinded neuroradiologists in terms of the level of diagnostic information, the type of additional information provided by post-contrast images, the best post-contrast image set in terms of diagnostic information, the radiological utility of MultiHance, and the detectability of brain metastases. Extensive safety and tolerability controls were performed at 3 and 24 h post-contrast. RESULTS: Additional diagnostic information was available on MultiHance-enhanced images as compared to pre-contrast images for 58.678.9% of patients administered 0.1 mmol/kg MultiHance and 66.1-74.6% of patients administered 0.2 mmol/kg MultiHance. Generally, the early (0 to 30 min) post-contrast image sets were preferred, with a clear superiority at the 15-30 min post-dose time point. In a subgroup of 21 patients with brain metastases, a higher number of lesions was detected in 55.6-66.7% of the cases with 0.1 mmol/kg MultiHance and in 58.3% of the cases with 0.2 mmol/kg MultiHance. Overall, the usefulness of MultiHance was judged as good to excellent in 91.4% of the patients at both dose levels. A total of 12 of 120 patients (10%) reported 15 transient, self-resolving adverse events of mild-to-moderate intensity. No difference between doses was observed in the incidence of adverse events and no laboratory, ECG or vital signs abnormalities were reported. CONCLUSION: MultiHance is a safe and effective contrast agent for magnetic resonance assessment of brain tumors when administered intravenously at doses up to 0.2 mmol/kg.

Neuroradiological features of intracranial and intraorbital meningeal haemangiopericytomas.

The neuroradiological features of six intracranial and one intraorbital haemangiopericytomas (HP) are reviewed. CT was performed before and after IV contrast medium in 5 patients. In 2 patients MRI was performed before and after contrast medium; in another, only unenhanced images were obtained. Five patients were studied by selective external and internal carotid artery angiography. Women constituted 5 of the 7 patients, and the mean age was 50.5 years, thus the sex and age distribution did not differ from that of typical meningiomas. Contrary to previous reports, calcification was present in two of the intracranial HP, and bone erosion was clearly seen in one intracranial HP and the orbital lesion. On MRI the tumours showed no differences from angioblastic meningiomas. All 6 intracranial HP were aggressive: all recurred following treatment and extracerebral metastasis occurred in one case.

Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic-pituitary and parasellar pathology.

OBJECTIVE: We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions. DESIGN: We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. PATIENTS: We studied 40 patients submitted for hypothalamic-pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated postoperatively. MEASUREMENTS: Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis. RESULTS: Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67.5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH-secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery. CONCLUSIONS: In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered.

[Intracranial hemorrhage in patients undergoing anticoagulant treatment with acenocoumarol]. / Hemorragia intracraneal en pacientes sometidos a tratamiento anticoagulante con acenocumarol.

Between 1980 and 1985, 2,012 patients treated with acenocoumarol were followed up. 31 of them had intracranial hemorrhage (ICH), representing an incidence of 1.54%. Its mortality rate was as high as 45%. The most common indication of anticoagulant therapy was cardiac valvular disease. No precipitating factors or concomitant hemorrhages in other sites were detected. Most patients with ICH were, at the time of the accident, within the therapeutic anticoagulant range. The most common localization of ICH was intraparenchymal; most of them developed after one year of anticoagulant therapy. In 32% of instances there was previous hypertension and previous stroke in 26%. ICH had a three times greater incidence in patients over 65 years. The patients who died showed larger hematomas than survivors in computed tomography.

CT appearance of low attenuation areas in basal ganglia in childhood: report of 23 cases.

Low attenuation areas were seen at CT in the basal ganglia of 23 patients aged less than 15 years. The relationship between CT images and pathological findings is investigated and the differential diagnosis is made.

Preoperative embolization of intracranial meningiomas.

The goal of preoperative embolization of intracranial meningiomas is to facilitate their surgical removal by reducing tumor vascularity and decreasing blood loss during surgery. This study is based on personal experience with about 100 embolized meningiomas and on the experience of others. Embolization is performed during the same session as diagnostic angiography. The appropriate embolic materials (absorbable or nonabsorbable) are chosen according to the location of the tumor, the size of the feeding arteries, the blood flow, and the presence of any potentially dangerous vessels (dangerous anastomoses between external carotid artery and internal carotid or vertebral arteries, arteries supplying the cranial nerves). Preoperative embolization appeared to be very useful in large tumors with pure or predominant external carotid artery supply (convexity meningiomas), in skull-base meningiomas, and in middle fossa and paracavernous meningiomas. It was also useful in falx and parasagittal meningiomas receiving blood supply from the opposite side and in posterior fossa meningiomas. CT low densities demonstrated after embolization did not always correlate with necrosis on microscopic examination, and large areas of infarction could be found despite normal CT. Embolic material was found on pathologic examination in 10%-30% of cases; fresh or recent ischemic and/or hemorrhagic necrosis consistent with technically successful embolization was demonstrated in 40%-60% of cases. With careful technique complications are rare.

Ventricular enlargement in young chronic schizophrenics.

The ventricular brain ratio (VBR) was measured in a group of 33 young in-patient schizophrenics and 25 controls. Results confirmed significant lateral ventricular enlargement in the schizophrenic patients, but could not demonstrate any association between the VBR and age or length of illness. Some aspects of the studied sample are discussed.