A Radiologist's Guide to the 2021 WHO Central Nervous System Tumor Classification: Part 2-Newly Described and Revised Tumor Types.

The fifth edition of the World Health Organization classification of tumors of the central nervous system (CNS), published in 2021, introduces major shifts in the classification of brain and spine tumors. These changes were necessitated by rapidly increasing knowledge of CNS tumor biology and therapies, much of which is based on molecular methods in tumor diagnosis. The growing complexity of CNS tumor genetics has required reorganization of tumor groups and acknowledgment of new tumor entities. For radiologists interpreting neuroimaging studies, proficiency with these updates is critical in providing excellent patient care. This review will focus on new or revised CNS tumor types and subtypes, beyond infiltrating glioma (described in part 1 of this series), with an emphasis on imaging features.

Ectopic orbital brain tissue: a case report with radiographic and clinical review.

Orbital heterotopic brain tissue is a rare entity with heterogenous clinical features requiring a multi-faceted diagnostic approach. The authors present a case of ectopic orbital brain tissue in an infant with a comprehensive literature review to highlight the radiographic findings of these lesions. Imaging findings are variable but describe well-circumscribed homogenous lesions with variable enhancement, without communication intracranially. The combination of computed tomography and magnetic resonance imaging can identify associated bony abnormalities, lesion-specific features, and effects on surrounding structures, which in combination with the clinical exam can be a valuable diagnostic and surveillance tool. Although ectopic orbital brain tumors are benign with excellent outcomes following complete resection, conservative management with observation and serial imaging may be an alternative method of management in patients with mild, non-vision threatening, non-distorting tumors.

A Radiologist's Guide to the 2021 WHO Central Nervous System Tumor Classification: Part I-Key Concepts and the Spectrum of Diffuse Gliomas.

The fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system, published in 2021, contains substantial updates in the classification of tumor types. Many of these changes are relevant to radiologists, including "big picture" changes to tumor diagnosis methods, nomenclature, and grading, which apply broadly to many or all central nervous system tumor types, as well as the addition, elimination, and renaming of multiple specific tumor types. Radiologists are integral in interpreting brain tumor imaging studies and have a considerable impact on patient care. Thus, radiologists must be aware of pertinent changes in the field. Staying updated with the most current guidelines allows radiologists to be informed and effective at multidisciplinary tumor boards and in interactions with colleagues in neuro-oncology, neurosurgery, radiation oncology, and neuropathology. This review represents the first of a two-installment review series on the most recent changes to the WHO brain tumor classification system. This first installment focuses on the changes to the classification of adult and pediatric gliomas of greatest relevance for radiologists.

Imaging Findings of Pediatric Orbital Masses and Tumor Mimics.

Pediatric orbital masses are not common but encompass a wide spectrum of benign and malignant entities that range from developmental anomalies to primary and secondary orbital malignancies and metastatic disease. Certain orbital tumors are unique to pediatric patients, such as retinoblastoma and neuroblastoma. Clinical symptoms and signs are often insufficient to differentiate between orbital lesions, and imaging is essential for narrowing the diagnostic considerations and determining the most appropriate management strategy. MRI is the primary imaging modality for evaluating orbital masses in children, with US and CT playing complementary roles. The authors review a spectrum of masses and tumor mimics that affect the pediatric globe and orbit. The shared and differentiating characteristics of pediatric orbital lesions are reviewed. Emphasis is placed on utilizing an orbital compartment-based approach to narrow the differential diagnosis. By using this organizational scheme, the authors describe intraocular processes (retinoblastoma, persistent fetal vasculature, and Coats disease), intraconal lesions (lymphatic malformation, schwannoma, optic nerve sheath meningioma, and optic pathway glioma), extraconal lesions (infantile hemangioma, rhabdomyosarcoma, idiopathic orbital inflammation, lymphoma, venous varix, plexiform neurofibroma, and pleomorphic adenoma of the lacrimal gland), and lesions involving the bony orbit (dermoid cyst, metastatic neuroblastoma, and Langerhans cell histiocytosis). The authors describe the basic management of each entity. Orbital infections and traumatic lesions are beyond the scope of this article. ©RSNA, 2022.

Comparison of 1.5 Tesla and 3.0 Tesla Magnetic Resonance Imaging in the Evaluation of Acute Demyelinating Optic Neuritis.

BACKGROUND: Optic neuritis (ON) is the most common optic neuropathy in young adults. MRI is reported to have a high sensitivity for ON. Higher signal strengths of MRI may enhance resolution and lead to better detection of ON. We sought to compare the sensitivity of 3.0 Tesla (T) MRI to that of 1.5 T MRI in detecting acute demyelinating ON. METHODS: A retrospective chart review was performed on patients with a clinical diagnosis of optic neuritis at Mayo Clinic Health System from January 2010 to April 2020. Among 1,850 patients identified, 126 patients met the eligibility criteria. Exclusion criteria comprised questionable or alternative diagnosis, diagnosis of ON before the study period, eye examinations performed elsewhere, or absence of fat-saturated head and orbits MRIs performed locally within 30 days of symptom onset. Gadolinium contrast enhancement, T2 hyperintensity, and the radiologic diagnosis of ON were recorded by a neuro-radiologist who was masked to the clinical history and the magnet strength of the MRI. RESULTS: Fifty-three patients (42.1%) had 3.0 T MRI, and 73 patients (57.9%) had 1.5 T MRI. Overall, 88.9% (112/126) of patients were determined to have a positive MRI for ON. The radiographic sensitivity for ON was higher in the 3.0 T group compared with the 1.5 T group (98.1% vs 82.2%, respectively [ P = 0.004]). The frequency of gadolinium enhancement was found to be greater in the 3 T group compared with the 1.5 T group (98.1% vs 76.7%, respectively [ P < 0.001]). T2 hyperintensity was also more often seen in the 3.0 T group compared with the 1.5 T group (88.7% vs 68.5%, respectively [ P = 0.01]). CONCLUSIONS: 3.0 T MRI is more sensitive than 1.5 T MRI in detecting ON. This finding suggests that 3.0 T MRI is a preferred imaging modality for the confirmation of ON.

Pediatric Myxopapillary Ependymomas: A Clinicopathologic Evaluation.

Myxopapillary ependymomas (MPEs) have an indolent clinical course, corresponding to World Health Organization Grade I. A total of 13 pediatric MPEs have been reported in the literature with "anaplastic features," including elevated proliferative activity (≥5 mitoses/10 high-power fields), necrosis, and microvascular proliferation. No consensus exists regarding the prognostic significance of such features. A retrospective clinicopathologic review of pediatric MPEs diagnosed between 1996 and 2018 at Mayo Clinic was performed. Totally, 8 pediatric MPEs (6 male; age: 7.52 to 16.88 y) were identified. Totally, 3 had disseminated disease at presentation. All patients underwent surgical resection (7 gross total; 1 subtotal). Totally, 5 cases harbored ≥5 mitoses/10 high-power fields (range: 5 to 9), 3 of which showed necrosis (2 with disseminated disease). Postsurgery, 2 patients received radiation; one with disseminated disease and another with increased mitotic activity/necrosis; neither has recurred (follow-up: 1.18 and 3.19 y). In all, 2 patients with disseminated disease, elevated mitotic activity, and necrosis had new metastatic disease/progression of nonresected metastatic foci (2.6 and 26.8 mo), received radiation therapy, and remain progression free (3.01 and 9.34 y). All patients are alive (median follow-up 1.31 y, range: 0.66 to 11.75). Among pediatric MPEs, the concurrent presence of elevated mitotic activity and necrosis may be associated with an aggressive clinical course, warranting closer surveillance and consideration of adjuvant therapies.

Intracranial Pure Germinoma With Optic Nerve Infiltration.

A 19-year-old man presented with a 3-year history of episodic headaches, right hemiparesis, and progressive vision loss in both eyes. Initially, extensive laboratory testing was unrevealing. MRI later demonstrated progressive enlargement and enhancement of the left optic nerve poorly correlated with the timing of his clinical manifestations. There was no clinical or radiological response to treatment with corticosteroids, mycophenolate mofetil, or rituximab administered empirically for possible inflammatory processes. Later in the disease course, he developed diabetes insipidus (DI), worsening vision to light perception bilaterally, severe cognitive decline, and spastic quadriparesis. Cerebrospinal fluid (CSF) beta human chorionic gonadotropin (ß-hCG) was elevated. Eventually, a left optic nerve biopsy was performed, which was consistent with an intracranial pure germinoma with infiltration of the optic nerve and disseminated leptomeningeal disease. Although rare, intracranial germ cell tumors can primarily involve the anterior visual pathways and should be considered in the setting of DI and elevated CSF ß-hCG.

Carotid Cavernous Fistula Mimicking Hemicrania Continua: A Case Report.

BACKGROUND: Hemicrania continua is a primary headache disorder characterized by a continuous, unilateral headache associated with ipsilateral cranial autonomic features that responds to indomethacin. By definition, the symptoms are not referable to an underlying structural pathology. However, several cases of secondary hemicrania continua related to underlying structural lesions have been reported. CASE: We present a case of a 53-year-old male with a prolonged, right-sided headache associated with intermittent right-sided ptosis, conjunctival injection, tearing, and nasal congestion, suggestive of hemicrania continua, who was found to have an indirect carotid-cavernous fistula, and who, after endovascular treatment of the fistula, had resolution of his symptoms. CONCLUSION: Alternative, and perhaps less common, causes of headache should be considered when the clinical presentation is atypical or does not clearly fulfill diagnostic criteria for primary headache disorders. Carotid cavernous fistulas should be included within this differential, and represent a potentially treatable and reversible cause of otherwise refractory headache.

Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study.

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.

MRI screening of the internal auditory canal: Is gadolinium necessary to detect intralabyrinthine schwannomas?

OBJECTIVE: Non-contrast MRI of the internal auditory canal (IAC) using high-resolution T2WI (T2 weighted image) has been proposed as the primary screening study in patients with sudden or asymmetric sensorineural hearing loss (ASNHL). However, there are concerns that non-contrast MRI may not detect labyrinthine pathology, specifically intralabyrinthine schwannomas (ILSs). The purpose of this study was to determine if non-contrast high-resolution T2WI alone are adequate to exclude these uncommon intralabyrinthine tumors. METHODS: 31 patients with ILSs and 36 patients without inner ear pathology that had dedicated MRI of the IAC performed with both non-contrast T2WI and post-contrast T1WI (T1 weighted image) were identified. Three board-certified neuroradiologists reviewed only the T2WI from these 67 cases. When an ILS was identified, its location and size were recorded. Sensitivity, specificity, and accuracy were calculated using the post-contrast T1WI as the "gold standard." A consensus review of cases with discordant results was conducted. RESULTS: The sensitivity, specificity, and accuracy were 1.0, 1.0, and 1.0 for Observer 1; 0.84, 1.0, and 0.96 for Observer 2; 0.90, 1.0, and 0.98 for Observer 3. The 5 ILSs with discordant results were correctly identified upon consensus review. The median size of the ILSs was 4.4mm (±2.9mm) and most (18/31) were intracochlear in location. CONCLUSION: Non-contrast high-resolution T2WI alone can detect ILSs with 84-100% sensitivity, suggesting that gadolinium may be unnecessary to exclude ILSs on screening MRI. These findings have implications for reducing cost, time, and adverse events associated with gadolinium administration in patients presenting with sudden or ASNHL. LEVEL OF EVIDENCE: 4.

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. © RSNA, 2017.

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. © RSNA, 2017 Online supplemental material is available for this article.

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.

Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor.

Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly occur in children and rarely in adults. Because of the rarity of this tumor, its outcomes and prognostic variables are not well characterized. The purpose of this study was to evaluate clinical outcomes and prognostic factors for children and adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method, and relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk stratification (standard vs. high) and age, the increased risk of disease recurrence in adults persisted. A nonsignificant tendency toward poorer OS in adult patients relative to pediatric patients also persisted. High-dose chemotherapy with stem cell rescue was associated with a statistically significant improvement in OS and a tendency toward improved DFS, although the findings were mitigated when the effect of age was considered. Local recurrence was the primary pattern of treatment failure in both adults and children. Our results suggest that adult patients with CNS PNETs have inferior outcomes relative to the pediatric cohort. Further research is needed to improve outcomes for CNS PNET in populations of all ages.

Pituitary volume changes in pregnancy and the post-partum period.

PURPOSE: Imaging changes in the pituitary volume during pregnancy remains scantly researched. This study set out to assess the differences in total, anterior, and posterior pituitary volume in pregnant women compared to nulliparous and post-partum women. MATERIALS AND METHODS: A retrospective review was completed of women that had undergone MRI imaging of the brain. Patients were divided into three cohorts: pregnant, nulliparous, and post-partum (defined as being within 12 months of delivery). Anterior and posterior pituitary volumes were manually measured. RESULTS: 171 patients were included, of which 68 were pregnant, 52 were post-partum, and 51 were nulliparous. The average anterior (621.0 ± 171.6 mm3) and total (705.4 ± 172.2 mm3) pituitary volumes were significantly larger in pregnant patients than nulliparous women (522.6 ± 159.8 mm3 and 624.5 ± 163.7 mm3, respectively) (p = .002 and p = .01, respectively). The posterior pituitary volume was significantly smaller in pregnant women (84.4 ± 32.9 mm3) compared to both post-partum (101.2 ± 42.0 mm3) and nulliparous (102.0 ± 46.1 mm3) women (p = .02 for both). CONCLUSIONS: The anterior and total pituitary volumes are significantly larger during pregnancy persisting into the post-partum period. The posterior pituitary volume, conversely, decreases during pregnancy, and returns to its normal size in the post-partum period.

Radiology-pathology correlation: Giant tumefactive perivascular spaces.

Dilated perivascular spaces (PVSs) are common and easily recognized on imaging. However, rarer giant tumefactive PVSs (GTPVSs) can have unusual multilocular cystic configurations, and are often confused for other pathologic entities, including neoplasms, cystic infarctions, and neuroepithelial cysts. Because GTPVSs are scarcely encountered and even more infrequently operated upon, many radiologists are unaware of the imaging and pathologic features of these lesions. Here, a case of a resected GTPVS is presented, highlighting both its radiologic and histologic characteristics, and discussing how such lesions can be differentiated from their closest mimickers on imaging.

Dorsoventral splitting of the infundibulum in a child with pituitary hypoplasia.

Pituitary development arises from ectodermal tissue creating Rathke's pouch and ultimately the adenohypophysis anteriorly whereas neuroectodermal tissue arising from the diencephalon creates the neurohypophysis posteriorly. Alterations in pituitary development can lead to hormonal dysregulation and dysfunction. Following clinical suspicion of pituitary endocrinopathy, MRI plays a vital role in identifying and characterizing underlying structural abnormalities of the pituitary gland, as well as any associated extrapituitary findings. Here we report a case of an 18-month-old female presenting with short stature and growth hormone deficiency. MRI was notable for a shallow sella turcica, a hypoplastic adenohypophysis, thin pituitary stalk, and ectopic neurohypophysis. Interestingly, the pituitary stalk was noted to split dorsoventrally with a split pituitary bright spot and T1 hypointense lobe hypothesized to represent separation of the posterior pituitary lobes.