Laurence J. Eckel

Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging

PURPOSE To determine if repeated intravenous exposures to gadolinium-based contrast agents (GBCAs) are associated with neuronal tissue deposition. MATERIALS AND METHODS In this institutional review board-approved single-center study, signal intensities from T1-weighted magnetic resonance (MR) images and postmortem neuronal tissue samples from 13 patients who underwent at least four GBCA-enhanced brain MR examinations between 2000 and 2014 (contrast group) were compared with those from 10 patients who did not receive GBCA (control group). Antemortem consent was obtained from all study participants. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus of these 23 deceased patients were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Associations between cumulative gadolinium dose, changes in T1-weighted MR signal intensity, and ICP-MS-derived tissue gadolinium concentrations were examined by using the Spearman rank correlation coefficient (ρ). RESULTS Compared with neuronal tissues of control patients, all of which demonstrated undetectable levels of gadolinium, neuronal tissues of patients from the contrast group contained 0.1-58.8 μg gadolinium per gram of tissue, in a significant dose-dependent relationship that correlated with signal intensity changes on precontrast T1-weighted MR images (ρ = 0.49-0.93). All patients in the contrast group had relatively normal renal function at the time of MR examination. Gadolinium deposition in the capillary endothelium and neural interstitium was observed only in the contrast group. CONCLUSION Intravenous GBCA exposure is associated with neuronal tissue deposition in the setting of relatively normal renal function. Additional studies are needed to investigate the clinical significance of these findings and the generalizability to other GBCAs. Online supplemental material is available for this article.

Answers to Common Questions About the Use and Safety of CT Scans.

Articles in the scientific literature and lay press over the past several years have implied that computed tomography (CT) may cause cancer and that physicians and patients must exercise caution in its use. Although there is broad agreement on the latter point--unnecessary medical tests of any type should always be avoided--there is considerable controversy surrounding the question of whether, or to what extent, CT scans can lead to future cancers. Although the doses used in CT are higher than those used in conventional radiographic examinations, they are still 10 to 100 times lower than the dose levels that have been reported to increase the risk of cancer. Despite the fact that at the low doses associated with a CT scan the risk either is too low to be convincingly demonstrated or does not exist, the magnitude of the concern among patients and some medical professionals that CT scans increase cancer risk remains unreasonably high. In this article, common questions about CT scanning and radiation are answered to provide physicians with accurate information on which to base their medical decisions and respond to patient questions.

Long-term outcomes for low-grade intracranial ganglioglioma: 30-year experience from the Mayo Clinic

OBJECT Gangliogliomas comprise less than 1% of all brain tumors and occur most often in children. Therefore, there are a limited number of patients and data involving the use or role of adjuvant therapy after subtotal resections (STRs) of gangliogliomas. The objective of this study was to examine and review the Mayo Clinic experience of 88 patients with gangliogliomas, their follow-up, risk of recurrence, and the role of radiation therapy after STR or only biopsy. METHODS Eighty-eight patients with gangliogliomas diagnosed between 1970 and 2007 were reviewed. Data on clinical outcomes and therapy received were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival. RESULTS The median age at diagnosis was 19 years. The median potential follow-up as of June 2008 was 142 months (range 9-416 months). Fifteen-year overall survival was 94%, median PFS was 5.6 years, with a 10-year PFS rate of 37%. Progression-free survival was dramatically affected by extent of initial resection (p < 0.0001). CONCLUSIONS This single-institution retrospective series of patients with gangliogliomas is unique given its large cohort size with a long follow-up duration, and confirms the excellent long-term survival rate in this group. The study also shows the importance of resection extent on likelihood of recurrence. Patients with gangliogliomas who undergo STR or biopsy alone have poor PFS. Radiation therapy may delay time to progression in patients with unresectable disease.

Primary inner ear schwannomas: a case series and systematic review of the literature.

To describe the natural history of primary inner ear schwannomas (PIES) and evaluate management outcomes and relationship between PIES location, clinical presentation, and time to diagnosis.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m2) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety.

Intramedullary Spinal Cord Metastases: MRI and Relevant Clinical Features From a 13-Year Institutional Case Series

This article reviews the MRI and clinical findings in 70 spinal cord metastases; 20% of patients had multiple metastases and 8% were asymptomatic. Spinal cord metastases were the initial clinical presentation in 20% of patients. Nearly all metastases showed contrast enhancement and had extensive edema. Cysts and hemorrhage were, however, uncommon and nearly 60% of patients had other metastases to the CNS or that were seen in studies in other organs. Accompanying pial metastases were also common. BACKGROUND AND PURPOSE: Because intramedullary spinal cord metastasis is often a difficult diagnosis to make, our purpose was to perform a systematic review of the MR imaging and relevant baseline clinical features of intramedullary spinal cord metastases in a large series. MATERIALS AND METHODS: Consecutive patients with intramedullary spinal cord metastasis with available pretreatment digital MR imaging examinations were identified. The MR imaging examination(s) for each patient was reviewed by 2 neuroradiologists for various imaging characteristics. Relevant clinical data were obtained. RESULTS: Forty-nine patients had 70 intramedullary spinal cord metastases, with 10 (20%) having multiple intramedullary spinal cord metastases; 8% (4/49) were asymptomatic. Primary tumor diagnosis was preceded by intramedullary spinal cord metastasis presentation in 20% (10/49) and by intramedullary spinal cord metastasis diagnosis in 10% (5/49); 98% (63/64) of intramedullary spinal cord metastases enhanced. Cord edema was extensive: mean, 4.5 segments, 3.6-fold larger than enhancing lesion, and ≥3 segments in 54% (37/69). Intratumoral cystic change was seen in 3% (2/70) and hemorrhage in 1% (1/70); 59% (29/49) of reference MR imaging examinations displayed other CNS or spinal (non–spinal cord) metastases, and 59% (29/49) exhibited the primary tumor/non-CNS metastases, with 88% (43/49) displaying ≥1 finding and 31% (15/49) displaying both findings. Patients with solitary intramedullary spinal cord metastasis were less likely than those with multiple intramedullary spinal cord metastases to have other CNS or spinal (non–spinal cord) metastases on the reference MR imaging (20/39 [51%] versus 9/10 [90%], respectively; P = .0263). CONCLUSIONS: Lack of known primary malignancy or spinal cord symptoms should not discourage consideration of intramedullary spinal cord metastasis. Enhancement and extensive edema for lesion size (often ≥3 segments) are typical for intramedullary spinal cord metastasis. Presence of cystic change/hemorrhage makes intramedullary spinal cord metastasis unlikely. Evidence for other CNS or spinal (non–spinal cord) metastases and the primary tumor/non-CNS metastases are common. The prevalence of other CNS or spinal (non–spinal cord) metastases in those with multiple intramedullary spinal cord metastases is especially high.

Comparison of Gadolinium Concentrations within Multiple Rat Organs after Intravenous Administration of Linear versus Macrocyclic Gadolinium Chelates

Purpose To compare gadolinium tissue concentrations of multiple linear and macrocyclic chelates in a rat model to better understand the scope and extent of tissue deposition following multiple intravenous doses of gadolinium-based contrast agent (GBCA). Materials and Methods In this Institutional Animal Care and Use Committee-approved study, healthy rats received 20 intravenous injections of 2.5 mmol gadolinium per kilogram (gadolinium-exposed group) or saline (control group) over a 26-day period. Unenhanced T1 signal intensities of the dentate nucleus were measured from magnetic resonance (MR) images obtained prior to GBCA injection and 3 days after final injection. Rat brain and renal, hepatic, and splenic tissues were harvested 7 days after final injection and subjected to inductively coupled plasma mass spectrometry and transmission electron microscopy for quantification and characterization of gadolinium deposits. Results Gadolinium deposition in brain tissue significantly varied with GBCA type (F = 31.2; P < .0001), with median concentrations of 0 μg gadolinium per gram of tissue (95% confidence interval [CI]: 0, 0.2) in gadoteridol-injected rats, 1.6 μg gadolinium per gram of tissue (95% CI: 0.9, 4.7) in gadobutrol-injected rats, 4.7 μg gadolinium per gram of tissue (95% CI: 3.5, 6.1) in gadobenate dimeglumine-injected rats, and 6.9 μg gadolinium per gram of tissue (95% CI: 6.2, 7.0) in gadodiamide-injected rats; a significant positive dose-signal intensity correlation was identified (ρ = 0.93; P < .0001). No detectable neural tissue deposition or MR imaging signal was observed in control rats (n = 6). Similar relative differences in gadolinium deposition were observed in renal, hepatic, and splenic tissues at much higher tissue concentrations (P < .0001). Gadolinium deposits were visualized directly in the endothelial capillary walls and neural interstitium in GBCA-injected rats, but not in control rats. Conclusion Tissue deposition of gadolinium was two- to fourfold higher following administration of the linear agents gadodiamide and gadobenate dimeglumine compared with the macrocyclic agents gadobutrol and gadoteridol. These findings suggest that organ tissue deposition is reduced but not eliminated following administration of macrocyclic GBCA chelates in lieu of linear chelates.

Intracranial gadolinium deposition following gadodiamide-enhanced magnetic resonance imaging in pediatric patients: A case-control study

Intracranial Gadolinium Deposition Following Gadodiamide-Enhanced Magnetic Resonance Imaging in Pediatric Patients: A Case-Control Study Approximately 40% of the 3 million annual pediatric magnetic resonance imaging (MRI) examinations in the United States are performed with intravenous administration of a gadolinium-based contrast agent (GBCA).1 Contrastenhanced MRI provides critical clinical information that is often not apparent on unenhanced MRI or other imaging modalities. Notwithstanding their widespread use, studies demonstrating the unexpected accumulation of gadolinium within the neural tissues of adults following intravenous GBCA exposure have prompted ongoing investigations by the US Food and Drug Administration and European Medicines Agency regarding the safety and toxicity of these agents.2,3 Because these prior studies were limited to adults, the purpose of this study was to determine the extent of deposition in the GBCA-exposed population and whether prior observations were related to age-dependent breakdown of the blood-brain barrier through study of a cohort of pediatric patients who received gadodiamide-enhanced MRI examinations.

Rim and Flame Signs: Postgadolinium MRI Findings Specific for Non-CNS Intramedullary Spinal Cord Metastases

BACKGROUND AND PURPOSE: No highly specific MR imaging features distinguishing ISCMs from primary cord masses have been described. Our purpose was to retrospectively compare peripheral enhancement features on postgadolinium MR imaging of ISCMs with primary intramedullary cord masses. MATERIALS AND METHODS: A consecutive group of patients with firmly diagnosed ISCM (45 patients with 64 ISCMs) and a comparison group with consecutive pathologically proved primary intramedullary spinal cord masses (64 patients with 64 primary spinal cord masses: ependymoma, astrocytoma, hemangioblastoma, ganglioglioma, and cavernous malformation) were included. MR images were evaluated for 2 specific signs on postgadolinium images: a “rim” sign (more intense thin rim of peripheral enhancement around an enhancing lesion) and “flame” sign (ill-defined flame-shaped region of enhancement at the superior/inferior lesion margins). The frequency of rim and/or flame signs in ISCMs and primary cord masses was compared (χ2 test). For ISCMs, the maximal dimension of the enhancing lesion was correlated with the presence of rim or flame signs (t test). RESULTS: Rim and flame signs, alone and in combination, were seen more frequently in ISCMs than in primary cord masses (P < .0001 for each). Specificity and sensitivity, respectively, for diagnosing ISCMs among spinal cord masses on a per-patient basis were the following: rim sign, 97%, 47%; flame sign, 97%, 40%; at least 1 sign, 94%, 60%; and both signs concurrently, 100%, 27%. In the ISCM group, the presence of either a rim or flame sign correlated with a larger measured maximum enhancing lesion size (P = .0065 and P = .0012, respectively). CONCLUSIONS: The rim and flame signs are common in and specific for ISCM and are rare in primary spinal cord masses.

Position-related variability of CSF opening pressure measurements.

BACKGROUND AND PURPOSE: Normative data for CSF OP have previously been established with patients in the LD position. During fluoroscopically guided LP procedures, radiologists frequently obtain these OP measurements with patients prone. In this prospective study, our goal was to determine the variability of OP measurements as a function of patient positioning and to assess whether there is a relationship with patient BMI. MATERIALS AND METHODS: Consecutive patients reporting for fluoroscopically guided LP or myelography were enrolled. OP was measured with the patient in 3 positions, with the order of the technique randomized: prone with table flat, prone with table tilted until the hub of the needle was at the level of the right atrium, and LD with the needle hub at the level of the spinal canal. The BMI of each patient was calculated. The Wilcoxon signed-rank test and linear regression analysis with bivariate fit of difference were used for analysis. RESULTS: OP measurements with the patient in the prone position were significantly elevated compared with those in the LD position, with mean differences of 2.7 (P < .001) and 1.6 cm H2O, (P = .017) for prone flat and prone tilted, respectively. There was no significant difference in OP measurements for the prone flat versus prone tilted positions (P = .20). There was no correlation between BMI and observed differences (LD-flat: R2 = 0.00028; LD-tilt: R2 = 0.00038; prone-tilt: R2 = 0.00000020). CONCLUSIONS: Measuring OP with the patient in the prone position may result in overestimation of CSF pressure. Table tilt did not significantly impact mean prone OP. Radiologists should specify exact patient positioning when reporting OP measurements.