DisProt: intrinsic protein disorder annotation in 2020.

The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.

Real-world effectiveness of omalizumab for severe allergic asthma treatment in Colombia.

BACKGROUND: The allergic phenotype is responsible for more than 50% of severe asthma cases. In a stepwise approach, add-on treatments such as anti-IgE are used for severe allergic asthma (SAA). This study was aimed to describe the real-world effectiveness of omalizumab in adult and pediatric patients with SAA in Colombia. METHODS: This was an observational, non-interventional, retrospective study. Data from patients with SAA that received at least one month of treatment with omalizumab was obtained from medical records at eight sites in Colombia. Time-zero (t - 0) was defined as the date of initiation of omalizumab, and data was gathered for a 12-month period before t - 0 and a 12-month period after t - 0. Clinical outcomes, including exacerbations, were assessed at 6 and 12 months. Effectiveness of omalizumab was evaluated in terms of the reduction of the risk of exacerbations (annualized rate). RESULTS: We included 143 patients with SAA. There was a decrease of 72.4% of the annualized rate of clinically significant asthma exacerbations during the year after omalizumab (from 1.74 before to 0.48 after) with a substantial reduction of the risk of exacerbations by 56.7% (RR [95% CI] 0.43 [0.30-0.63] p < 0,001). CONCLUSION: The use of omalizumab in Colombia as a treatment for SAA notably reduced the risk of clinically significant exacerbations. This study is the first to evaluate omalizumab real-life effectiveness in pediatric and adult patients in the country.

Brain Abscess Apparent Diffusion Coefficient is Associated With Microbial Culture Yields.

BACKGROUND: Obtaining pus for microbial cultures is one of the surgical aims in patients with brain abscess. Predictors of microbial yields are necessary as they help in treatment planning. PURPOSE: To investigate the relationship between microbial culture yields of brain abscesses and their apparent diffusion coefficient (ADC) values and clinical characteristics. STUDY TYPE: Retrospective. SUBJECTS: Eighty-four patients diagnosed with brain abscess by surgery and histopathology (59 with positive abscess cultures). FIELD STRENGTH/SEQUENCE: Diffusion-weighted, T2-weigthed, and contrast-enhanced T1-weighted imaging at 1.5 T and 3 T. ASSESSMENT: Contrast-enhanced T1-weighted images were co-registered to ADC maps. Three neuroradiologists determined abscess imaging characteristics (distribution, location, and ventricular rupture), and two measured abscess volumes and ADC values. Clinical characteristics collected included sex, age, fever, underlying diseases, infection sources, white blood cell count, percentage of segmented neutrophils, C-reactive protein level, regimen and duration of empirical antibiotics, and types of surgery. STATISTICAL TESTS: Interobserver differences were assessed with Fleiss kappa and intraclass correlation coefficients. The differences in clinical and imaging factors between the positive and negative culture groups were compared with Chi-square analysis or Student's t test. All factors were subjected to multivariable logistic regression analysis to assess their associations with microbial culture yields, and factors with statistical significance were evaluated with receiver operating characteristic curve analysis to assess their diagnostic performance in discriminating the two groups. RESULTS: Mean ADC (×10-6  mm2 /s) of culture-negative abscesses (841 ± 173) was significantly higher (P < 0.05) than that of culture-positive abscesses (536 ± 90). On multivariable analysis, mean ADC was the only significant factor (P < 0.05) related to culture yields. With 660 as the cutoff value, the sensitivity, specificity, and accuracy of ADC for discriminating culture yields were 93.2%, 88.0%, and 91.7%, respectively. DATA CONCLUSION: ADC could be used to discriminate between culture-positive and culture-negative abscesses. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Peritumoral brain edema volume in meningioma correlates with tumor fractional anisotropy but not apparent diffusion coefficient or cerebral blood volume.

PURPOSE: Pathogenesis of peritumoral brain edema (PTBE) in meningiomas remains unclear. Associations between PTBE volume and diffusion or perfusion properties of meningioma have not been studied. We aimed to investigate if diffusion and perfusion properties of meningioma correlate with its PTBE volume. METHODS: Seventy consecutive patients (mean age, 58.9 ± 13.7 years; 37 women) with meningiomas who had preoperative DTI and DSC-PWI were retrospectively analyzed. PTBE volume, tumor volume, and mean T2 signal, ADC, FA, and CBV of the tumor were measured. Between meningiomas with and without PTBE, patient age and sex, as well as T2 signal intensity, volume, ADC, FA, and CBV of tumors, were compared. In meningiomas with PTBE, correlations of PTBE volume with patient age and sex, as well as T2 signal intensity, volume, ADC, FA, and CBV of tumors, were analyzed. Multivariable linear regression analysis was performed to identify factors associated with PTBE volume. RESULTS: On univariable analysis, meningiomas without PTBE were more frequently found in women (P = 0.033) and demonstrated lower ADC (P = 0.020), higher FA (P < 0.001), and lower CBV (P < 0.001). PTBE volume of meningiomas correlated with tumor ADC (r = 0.444; P = 0.001), tumor FA (r = - 0.655; P < 0.001), and tumor CBV (r = 0.402; P = 0.003). On multivariable analysis, tumor FA was the only factor associated with PTBE volume (P < 0.001). CONCLUSION: PTBE volume in meningioma correlates with tumor FA. DTI may help to understand the mechanism of PTBE in meningiomas.

Distinctive diffusion-weighted imaging features in late-onset genetic leukoencephalopathies.

Genetic leukoencephalopathies are inherited disorders characterized by progressive white matter involvement. Although most are paediatric conditions, late-onset adult leukoencephalopathies are being increasingly recognized. Adult leukoencephalopathies may present as neurodegenerative diseases with cognitive decline and motor symptoms. Similar to their paediatric counterparts, different adult leukoencephalopathies often have distinctive MRI appearances. In particular, DWI has been recently shown to demonstrate specific patterns of persistent diffusion restriction in several adult-onset leukoencephalopathies. As such, DWI may provide important clues to the diagnosis of adult-onset leukoencephalopathy. The purpose of this review is to discuss characteristic DWI features in some late-onset leukoencephalopathies.

Imaging of Neuronal and Mixed Glioneuronal Tumors.

Neuronal and mixed glioneuronal tumors represent a group of neoplasms with varying degrees of neural and glial elements. Their age of presentation varies, but they are most commonly seen in children and young adults. With the exception of anaplastic ganglioglioma and other atypical variants, most lesions are low grade; however, they can have significant morbidity because of seizures, mass effect, or difficult to treat hydrocephalus. Although many tumors show overlapping clinical and imaging features, some have relatively distinctive imaging characteristics that may aid in narrowing the differential diagnosis. In this review, we discuss relevant clinical and pathologic characteristics of these tumors and provide an overview of conventional and advanced imaging features that provide clues as to the diagnosis.

Hippocampal Sulcus Remnant: Common Finding in Nonelderly Adults on Ultra-High-Resolution 7T Magnetic Resonance Imaging.

OBJECTIVE: The objective of this study was to investigate the frequency of hippocampal sulcus remnants (HSRs) in nonelderly adults using ultra-high-resolution 7T magnetic resonance (MR) images and their imaging features. METHODS: A total of 33 healthy adults underwent 7T MR, and multiplanar images of 66 temporal lobes were reviewed independently by 2 neuroradiologists. The detectability of the HSR was calculated. In addition, the interobserver agreement on the rating scale was evaluated using the κ statistic. RESULTS: Both observers identified HSRs with 7T MR images in all subjects. Excellent interobserver agreement was shown (κ = 1.0). The shape of HSRs was variable (spot-like, curvilinear, ovoid, or beaded appearance). Volumes of the HSRs were not correlated with age. CONCLUSIONS: Hippocampal sulcus remnants are commonly seen in healthy nonelderly adults using 7T MR imaging. Accurate diagnosis of HSR based on the microanatomy of hippocampus makes it easier to differentiate them from lesions, and it may help prevent unnecessary treatment.

Baseline multicentric tumors, distant recurrences and leptomeningeal dissemination predict poor survival in patients with recurrent glioblastomas receiving bevacizumab.

PURPOSE: There are no widely accepted MRI markers that predict treatment outcomes of bevacizumab among patients with recurrent glioblastoma (GB). We aimed to determine if conventional MRI features of recurrent GB predict survival of patients receiving bevacizumab. METHODS: Patients with recurrent GB were retrospectively included if they received bevacizumab monotherapy between 2008 and 2017 after failure of standard treatment. Their MRI studies obtained at baseline and tumor recurrence, prior to bevacizumab treatment, were evaluated for multiple MRI features including measurable tumor, baseline multicentric tumors, distant recurrence, non-contrast-enhancing tumor, deep white matter invasion, multiple parenchymal tumors, bilateral cerebral involvement, ependymal extension and leptomeningeal dissemination. Predictive values of MRI features and patient characteristics on patient survival were statistically analyzed. RESULTS: A total of 103 patients were included. Baseline multicentric tumors (OR = 4.07; P = 0.042) and distant recurrence (OR = 28.5; P < 0.001) were two significant predictors of 3-month progression-free survival (PFS) rate. Distant recurrence (HR = 3.94; P < 0.001) was the only independent predictor of PFS. Baseline multicentric tumors (HR = 1.97; P = 0.028), distant recurrence (HR = 4.73; P < 0.001) and leptomeningeal dissemination (HR = 2.28; P = 0.044) were three independent predictors of overall survival. CONCLUSIONS: Baseline multicentric tumors, distant recurrence and leptomeningeal dissemination predicted poor survival among patients receiving bevacizumab for recurrent GB. Conventional MRI may help selecting patients with recurrent GB for bevacizumab treatment.

Novel Geographic Thematic Study of the Largest Radiology Societies Globally: How Is Gender Structure Biased Within Editorial Boards?

OBJECTIVE. Radiology has traditionally been a male-dominated medical specialty, and this is also reflected in the authorship of radiology publications and the composition of radiology journal editorial boards. The purpose of this study was to quantify the extent of the gender disparities reflected within the journal editorial boards of the largest international radiologic societies. MATERIALS AND METHODS. Methods were crafted to generate a geographically based gender analysis of the editorial boards of the largest general radiologic societies globally. All editorial board members of journals that were published by societies included in the study and that had an impact factor of 1 or greater were assessed to determine the gender composition of the board and the research productivity and career advancement of its members. Analyzed metrics included gender, academic rank, departmental leadership positions, subspecialty, total number of peer-reviewed publications, total number of citations, the h-index, and total number of years of active research. RESULTS. Significant gender disparity was noted across the six journal editorial boards included. Overall, 80.87% of editorial board members were men and 19.13% were women. Men were more prevalent than women across all academic ranks. Male editorial board members had longer publishing careers (22.5 vs 18 years; p = 0.015), a higher total number of publications (110 vs 65 publications; p < 0.001), and a higher h-index (25 vs 19; p < 0.001) than their female counterparts. Female editorial board members at higher academic ranks were less represented on editorial boards and were also less likely to have formal departmental leadership titles. CONCLUSION. Editorial boards have significant gender disparities, with no specific geographic regional variation noted. Male editorial board members published more, had higher h-indexes, and held more departmental leadership positions than their female counterparts.

DisProt 7.0: a major update of the database of disordered proteins.

The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as regions that are at least five consecutive residues without well-defined structure. We base our assessment of disorder strictly on experimental evidence, such as X-ray crystallography and nuclear magnetic resonance (primary techniques) and a broad range of other experimental approaches (secondary techniques). Confident and ambiguous annotations are highlighted separately. DisProt 7.0 presents classified knowledge regarding the experimental characterization and functional annotations of IDPs/IDRs, and is intended to provide an invaluable resource for the research community for a better understanding structural disorder and for developing better computational tools for studying disordered proteins.

Brain herniations into the dural venous sinus or calvarium: MRI findings, possible causes and clinical significance.

OBJECTIVES: To determine frequency, imaging features and clinical significance of herniations of brain parenchyma into dural venous sinuses (DVS) and/or calvarium found on MRI. METHODS: A total of 6160 brain MRI examinations containing at least one high-resolution T1- or T2-weighted sequence were retrospectively evaluated to determine the presence of incidental brain herniations into the DVS or calvarium. MRI sequences available for review were evaluated according to their capability to demonstrate these herniations. Patients' symptoms and clinical findings were recorded. RESULTS: Twenty-one (0.32 %) brain parenchyma herniations into the DVS (n = 18) or calvarium (n = 3) in 20 patients were detected. The most common locations of the herniations were the transverse sinuses (n = 13) and those involving inferior gyrus of the temporal lobe (n = 9). High-resolution T1- and T2-weighted sequences were equally useful in the detection of these brain herniations. According to clinical symptoms, brain herniations were considered to be incidental but headaches were present in nine patients. CONCLUSION: Brain herniations with surrounding cerebrospinal fluid (CSF) into the DVS and/or calvarium are incidental findings and not proven to be associated with any symptoms. Although rare, these herniations are more common than previously recognized and should not be confused with arachnoid granulations, clots or tumours. KEY POINTS: • Brain herniations into the DVS are more common than previously assumed. • The most frequent locations are the transverse sinus. • These herniations are incidental findings. • The relationship between brain herniation into DVS and headache is uncertain. • High-resolution MR sequences are most useful in detection of brain herniations.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide.

OBJECTIVES: To evaluate the impact of previous administration of gadodiamide and neural tissue gadolinium deposition in patients who received gadobenate dimeglumine. METHODS: Our population included 62 patients who underwent at least three administrations of gadobenate dimeglumine, plus an additional contrast-enhanced last MRI for reference, divided into two groups: group 1, patients who in addition to gadobenate dimeglumine administrations had prior exposure to multiple doses of gadodiamide; group 2, patients without previous exposure to other gadolinium-based contrast agent (GBCAs). Quantitative analysis was performed on the first and last gadobenate dimeglumine MRIs in both groups. Dentate nucleus-to-middle cerebellar peduncle signal intensity ratios (DN/MCP) and relative change (RC) in signal over time were calculated and compared between groups using generalized additive model. RESULTS: Group 1 showed significant increase in baseline and follow-up DN/MCP compared to group 2 (p < 0.0001). The RC DN/MCP showed a non-statistically significant trend towards an increase in patients who underwent previous gadodiamide (p = 0.0735). CONCLUSION: There is increased T1 signal change over time in patients who underwent gadobenate dimeglumine and had received prior gadodiamide compared to those without known exposure to previous gadodiamide. A potentiating effect from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur. KEY POINTS: • Neural gadolinium deposition is associated with multiple administrations of less stable GBCAs. • Less stable GBCA effect on subsequent more stable GBCA administrations is undetermined. • Significant increase of DN/MCP was seen in patients with previous gadodiamide exposure. • RC DN/MCP showed a non-significant increase in patients who received previous gadodiamide. • Potentiating effects from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur.

Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.

We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.

MIP Improves Detection of Brain Metastases.

PURPOSE: This study aimed to compare the sensitivity for detection of brain metastases using postcontrast 3-dimensional, T1W-gradient echo sequence (3DT1W) and maximum intensity projections (MIPs) obtained from the same data set. MATERIALS AND METHODS: A prospective analysis of patients with known brain metastases was performed. We compared 1-mm postcontrast 3DT1W with 6-mm MIP reconstructions obtained from the same images (MIP-3DT1) in 95 patients using 1.5 (42 patients) and 3 T (53 patient). Two independent readers analyzed all studies and the examinations were presented in anonymized and random fashion for a total of 190 interpretations per observer. One reader had more than 20 years of experience and the second reader had 1 year of experience. RESULTS: The least experienced observer found 542 brain metastases on postcontrast non-MIP 3DT1W and 605 with the MIP-3DT1 technique. For this observer, use of MIP resulted in increased number of detected metastases in 36% of patients regardless of field strength. The more experienced observer found 589 brain metastases on non-MIP 3DT1W and 621 with the MIP-3DT1 technique and the use of the latter also resulted in increased detection of metastases in 33% of patients regardless of field strength. CONCLUSIONS: In our study, we found that using MIP-3DT1 reconstructions of previously obtained postcontrast 3DT1W improved detection of brain metastases. This improvement was experienced by both the junior and experienced neuroradiologists and was also better at 3.0 T than at 1.5 T.

Use of Susceptibility-Weighted Imaging (SWI) in the Detection of Brain Hemorrhagic Metastases from Breast Cancer and Melanoma.

PURPOSE: Susceptibility-weighted imaging (SWI) has significantly increased our sensitivity in detecting hemorrhagic brain lesions. We sought to explore the prevalence of intratumoral hemorrhage as detected by SWI in brain metastases from melanoma and breast cancer. METHODS: Lesions with a size of 0.1 cm were categorized as micrometastases, whereas larger lesions were categorized as macrometastases. Susceptibility-weighted imaging findings on locations corresponding to enhancing lesions were categorized as either positive or negative based on presence/absence of signal dropout. The percentage of SWI positivity was then estimated as a function of lesion size. Two-tailed Fisher exact test was performed to examine differences in the contingency tables. RESULTS: Magnetic resonance imaging studies from 73 patients with 1173 brain metastases, which enhanced on postcontrast T1-weighted imaging (T1WI) were selected for analysis. Of these lesions, 952 had SWI data available, and 342 of 952 were micrometastases. Only 10 of the 342 micrometastases and 410 (67.2%) of the 610 macrometastases were SWI positive (P < 0.0001). When examined by tumor type, 76.9% (melanoma) versus 55.6% (breast cancer) were SWI positive (P < 0.0001), regardless of tumor size. All melanoma lesions (8/8) and only 1 of 15 breast cancer lesions larger than 1.5 cm were SWI positive. CONCLUSION: With the use of combined SWI and contrast-enhanced high-resolution T1 imaging, we found that presence of intratumoral brain hemorrhage is uncommon in micrometastases but common in metastases greater than 0.1 cm from breast cancer or melanoma. Large metastases commonly harbored hemorrhage, and this occurred more frequently in patients with melanoma than with breast cancer.

High Signal Intensity in Globus Pallidus and Dentate Nucleus on Unenhanced T1-weighted MR Images: Evaluation of Two Linear Gadolinium-based Contrast Agents.

PURPOSE: To determine if a correlation exists between the number of previous enhanced magnetic resonance (MR) imaging examinations and high signal intensity in the globus pallidus (GP) and dentate nucleus (DN) in patients who received gadodiamide (Omniscan), a linear nonionic gadolinium-based contrast agent, and in those who received gadobenate dimeglumine (MultiHance), a linear ionic contrast agent. MATERIALS AND METHODS: Institutional review board approval was obtained for this single-center retrospective study, with waiver of informed consent. The study population included 69 patients divided into two groups: Group 1 included patients who underwent gadodiamide-enhanced MR imaging, and group 2 included patients who underwent gadobenate dimeglumine-enhanced MR imaging. Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The GP-to-thalamus (TH) signal intensity ratio, DN-to-middle cerebellar peduncle (MCP) signal intensity ratio and relative percentage change (Rchange) between the first and last examinations for each patient were calculated. Relation between the signal intensity ratios and Rchange and the number of enhanced MR imaging examinations was analyzed by using a generalized additive model. Inter- and intraobserver agreement was evaluated with the Lin concordance correlation coefficient test. RESULTS: Group 1 included 23 patients (19 female), with a mean of 5.0 doses ± 2.4 (standard deviation) (range, 3-11 doses) administered. Group 2 included 46 patients (24 female) with a mean of 4.6 doses ± 2.2 (range, 3-11 doses) administered. The interval between the first and last examination was 1500.1 days ± 780.2 (range, 98-3097 days) for group 1 and 1086.2 days ± 582.9 (range, 94-2633) for group 2. All patients had normal liver and renal function. Gadodiamide showed a significant increase in DN:MCP and GP:TH (P < .001 for both) and in Rchange (P = .001 for GP:TH, P < .001 for DN:MCP). In group 2, there was no significant increase in DN:MCP or GP:TH over time or in Rchange for GP:TH, but there was a significant trend toward an increase in Rchange for DN:MCP (P = .013). Interobserver agreement was almost perfect (0.99; 95% confidence interval: 0.99, 0.99) for all evaluated structures. Intraobserver agreement was substantial to almost perfect for both readers. CONCLUSION: A significant increase in GP:TH and DN:MCP is associated with multiple gadodiamide-enhanced studies but not with gadobenate dimeglumine-enhanced studies, likely reflecting differences in stability and elimination of both contrast agents. Rate-of-change data indirectly suggest gadolinium deposition in the DN with gadobenate dimeglumine use, although it is considerably less than that with gadodiamide use.

Synonymous constraint elements show a tendency to encode intrinsically disordered protein segments.

Synonymous constraint elements (SCEs) are protein-coding genomic regions with very low synonymous mutation rates believed to carry additional, overlapping functions. Thousands of such potentially multi-functional elements were recently discovered by analyzing the levels and patterns of evolutionary conservation in human coding exons. These elements provide a good opportunity to improve our understanding of how the redundant nature of the genetic code is exploited in the cell. Our premise is that the protein segments encoded by such elements might better comply with the increased functional demands if they are structurally less constrained (i.e. intrinsically disordered). To test this idea, we investigated the protein segments encoded by SCEs with computational tools to describe the underlying structural properties. In addition to SCEs, we examined the level of disorder, secondary structure, and sequence complexity of protein regions overlapping with experimentally validated splice regulatory sites. We show that multi-functional gene regions translate into protein segments that are significantly enriched in structural disorder and compositional bias, while they are depleted in secondary structure and domain annotations compared to reference segments of similar lengths. This tendency suggests that relaxed protein structural constraints provide an advantage when accommodating multiple overlapping functions in coding regions.

History and evolution of brain tumor imaging: insights through radiology.

This review recounts the history of brain tumor diagnosis from antiquity to the present and, indirectly, the history of neuroradiology. Imaging of the brain has from the beginning held an enormous interest because of the inherent difficulty of this endeavor due to the presence of the skull. Because of this, most techniques when newly developed have always been used in neuroradiology and, although some have proved to be inappropriate for this purpose, many were easily incorporated into the specialty. The first major advance in modern neuroimaging was contrast agent-enhanced computed tomography, which permitted accurate anatomic localization of brain tumors and, by virtue of contrast enhancement, malignant ones. The most important advances in neuroimaging occurred with the development of magnetic resonance imaging and diffusion-weighted sequences that allowed an indirect estimation of tumor cellularity; this was further refined by the development of perfusion and permeability mapping. From its beginnings with indirect and purely anatomic imaging techniques, neuroradiology now uses a combination of anatomic and physiologic techniques that will play a critical role in biologic tumor imaging and radiologic genomics.

Imaging spectrum of CNS vasculitis.

Cerebral vasculitis is characterized by inflammation of the walls of blood vessels and may affect vessels of any size. The pathogenesis of vasculitis remains poorly understood. Vasculitis may affect large vessels (Takayasu arteritis, giant cell arteritis), medium-sized vessels (Kawasaki disease, polyarteritis nodosa), small vessels (immunoglobulin A vasculitis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis), or variable-sized vessels (Behçet disease, Cogan syndrome). Primary angiitis of the central nervous system (CNS) is an idiopathic disorder with no evidence of generalized inflammation that may simulate reversible cerebral vasoconstriction syndromes. Vasculitis may be secondary to systemic disease, infection, malignancy, drug use, or radiation therapy. Imaging findings vary from small ischemic changes to frank infarction, hemorrhage, and white matter edema and may show contrast material enhancement. The cerebral arteries may demonstrate a beaded appearance with variable degrees of stenosis, occlusion, and contrast enhancement of the vessel wall. Correlation of imaging findings with clinical presentation and laboratory test results helps establish the diagnosis of CNS vasculitis.