Asynchrony in Peritumoral Resting-State Blood Oxygen Level–Dependent fMRI Predicts Meningioma Grade and Invasion

BACKGROUND AND PURPOSE:Meningioma grade is determined by histologic analysis, with detectable brain invasion resulting in a diagnosis of grade II or III tumor. However, tissue undersampling is a common problem, and invasive parts of the tumor can be missed, resulting in the incorrect assignment of a lower grade. Radiographic biomarkers may be able to improve the diagnosis of grade and identify targets for biopsy. Prior work in patients with gliomas has shown that the resting-state blood oxygen level–dependent fMRI signal within these tumors is not synchronous with normal brain. We hypothesized that blood oxygen level–dependent asynchrony, a functional marker of vascular dysregulation, could predict meningioma grade.MATERIALS AND METHODS:We identified 25 patients with grade I and 11 patients with grade II or III meningiomas. Blood oxygen level–dependent time-series were extracted from the tumor and the radiographically normal control hemisphere and were included as predictors in a multiple linear regression to generate a blood oxygen level–dependent asynchrony map, in which negative values signify synchronous and positive values signify asynchronous activity relative to healthy brain. Masks of blood oxygen level–dependent asynchrony were created for each patient, and the fraction of the mask that extended beyond the contrast-enhancing tumor was computed.RESULTS:The spatial extent of blood oxygen level–dependent asynchrony was greater in high (grades II and III) than in low (I) grade tumors (P < 0.001) and could discriminate grade with high accuracy (area under the curve = 0.88).CONCLUSIONS:Blood oxygen level–dependent asynchrony radiographically discriminates meningioma grade and may provide targets for biopsy collection to aid in histologic diagnosis.

The 2016 World Health Organization guidelines for meningiomas were notable for the inclusion of brain invasion as a criterion sufficient for assignment to “high-grade” status (ie, grade II or III) and may explain the greater incidence of high-grade meningiomas since 2016.¹ In addition to brain invasion, a meningioma is considered grade II or III if it demonstrates an elevated mitotic index and ≥3 aggressive histologic features or demonstrates a loss of meningothelial differentiation.² While roughly 80% of all meningiomas are grade I, with excellent prognosis following surgical resection, the remaining 20% are grade II or III and more likely to recur.³ Furthermore, grade I tumors have a 10-year survival of 83%, compared with 61% for grade II and III tumors,⁴ making the accurate determination of meningioma grade important for both prognostic and treatment purposes.Histologic assessment remains the criterion standard for grading meningiomas; however, an accurate noninvasive prediction of tumor grade could benefit both clinicians and patients by improving preoperative planning and patient counseling and potentially guiding difficult management decisions. Furthermore, routine surgical biopsy may undersample regions that have histologic features, such as invasion, that are diagnostic for grade II or III meningioma, resulting in possible misdiagnosis. Identifying radiographic features that correlate with tumor invasion would, therefore, be useful for guiding biopsy location. Prior studies using standard-of-care structural imaging have attempted to predict meningioma grade by evaluating a mix of objective radiographic features, such as mean voxel intensity, and subjective radiographic features, such as the presence of hyperostosis.⁵ Peritumoral edema detected by T2-FLAIR has also been associated with higher-grade meningiomas.^6,7 Additionally, histogram analysis of diffusion tensor imaging has also been shown to correlate with tumor grade and tumor subtype in meningiomas.⁸ However, it would be beneficial to develop a single, simple, visual criterion that could be easily applied by radiologists and surgeons to predict meningioma grade with high accuracy.Prior work using resting-state blood oxygen level—dependent (BOLD) fMRI in diffuse glioma has revealed that the BOLD signal in and around the tumor is temporally asynchronous with radiographically normal parts of the brain.⁹ BOLD asynchrony maps provide a quantitation of this phenomenon and are generated by comparing each voxel with the mean global signal intensity of both the contralesional hemisphere and the contrast-enhancing tumor. Stereotactically localized biopsies collected from peritumoral regions have demonstrated that the degree of BOLD asynchrony correlates with local tumor burden.¹⁰ Furthermore, the spatial extent of the asynchrony can discriminate IDH wild-type and IDH-mutated gliomas with high fidelity.¹¹Meningiomas have also been shown to cause disruptions in vascular function observable with resting-state BOLD fMRI.¹¹ We, therefore, hypothesized that brain invasion, a common feature of high-grade meningiomas, would be detectable using BOLD asynchrony maps derived from resting-state BOLD fMRI and that the spatial extent of BOLD asynchrony could be used to discriminate meningioma grade. Furthermore, we evaluated whether combining the spatial features of BOLD asynchrony and T2-FLAIR hyperintensity could improve tumor grading accuracy over either measure alone.     

Pretreatment ADC Values Predict Response to Radiosurgery in Vestibular Schwannomas

BACKGROUND AND PURPOSE:The response rate of vestibular schwannomas to radiation therapy is variable, and there are surgical options available in the event of treatment failure. The aim of this study was to determine whether pre- and posttreatment ADC values can predict the tumor response to radiation therapy.MATERIALS AND METHODS:From a data base of 162 patients with vestibular schwannomas who underwent radiation therapy with gamma knife, CyberKnife, or fractionated stereotactic radiation therapy as the first-line therapy between January 2003 and December 2013, we found 20 patients who had pretreatment ADC values. There were 108 patients (including these 20) had serial MR images that included DWI allowing calculated ADC values from 2–132 months after radiation therapy. Two reviewers measured the mean, minimum, and maximum ADC values from elliptical ROIs that included tumor tissue only. Treatment responders were defined as those with a tumor total volume shrinkage of 20% or more after radiation therapy.RESULTS:The pretreatment mean minimum ADC for nonresponders was 986.7 × 10⁻⁶ mm²/s (range, 844–1230 × 10⁻⁶ mm²/s) and it was 669.2 × 10⁻⁶ mm²/s (range, 345–883 × 10⁻⁶ mm²/s) for responders. This difference was statistically significant (P < .001). Using a minimum ADC value of 800 × 10⁻⁶ mm²/s led to the correct classification of 18/20 patients based on pretreatment ADC values. The intraclass correlation between reviewers was 0.61. No posttreatment ADC values predicted response.CONCLUSIONS:Pretreatment ADC values of vestibular schwannomas are lower in responders than nonresponders. Using a minimum ADC value of 800 × 10⁻⁶ mm²/s correctly classified 90% of cases.

Tumors localized in the cerebellopontine angle comprise 5%–10% of all intracranial tumors.¹ Vestibular schwannomas (VSs) are the most common tumors in the cerebellopontine angle, accounting for 80% of all tumors there.^2,3 Epidemiologic data of VSs suggest the most common patients to be white and aged 50–60 years, with equal distribution between the sexes.⁴The diagnosis of VS is suggested by symptoms that may include tinnitus, hearing loss, trigeminal neuropathy, facial nerve palsy, unstable gait, or increased intracranial pressure.^5,6 High-resolution MR imaging has led to a greater number of smaller VSs being diagnosed in recent decades.⁷Few studies have evaluated the appearance of vestibular schwannomas on DWI. Chuang and colleagues⁸ have proposed that high ADCs of VSs may correlate with Antoni type B, which is associated with a cystic tumor pattern. However, this correlation is still controversial because the reviewed literature has not proved the correlation between Antoni type dominance and cystic composition.⁹ Tumors with sparse cellularity (Antoni B type) are associated with higher ADC values compared with tumors with an attenuated cellularity.¹⁰The options for managing VS include observation, surgery, and radiation therapy.^11–14 Usually, newly diagnosed and small VSs are managed expectantly with serial imaging follow-up and observation because many tumors remain stable over long periods of time. However, up to half of the tumors grow within 5 years of follow-up.¹⁵ Studies also state, however, that a wait-and-see policy is not recommended for patients with cystic tumors^16,17 because they tend to be larger and usually have a more rapid clinical evolution.^6,18 Specifically, for cystic VS, surgical treatment is the best option, and it is associated with better results than radiosurgery.¹ Other than in this cystic VS scenario, where the recommendation is firm, patient preference becomes paramount in the selection between surgery and radiosurgery for treatment. Both are considered appropriate, with similarly acceptable side effects and long-term success. The decision may be guided by multiple variables, such as the size at initial diagnosis, tumor growth rate on serial imaging, or patient symptoms.^7,19 More reliable patient-specific predictors of outcome with therapy are needed to guide patients and physicians in this important decision.ADC is a measure of the random motion of water molecules within a tissue, and it is calculated by using data from DWI or DTI.^20,21 ADC values have been shown to be correlated with astrocytoma tumor grading and tumor cellularity.^19,20 ADC measurements may serve as diagnostic and prognostic biomarkers as well as predictors of tumor response to treatment in glial tumors.^22,23 Thus, ADC values are often used in treatment planning.²⁴The aim of this study was to determine whether the pre- and posttreatment ADC values may be associated with the response of VS to radiosurgery and to provide guidance for further study.     

Evaluation of Diffusivity in the Anterior Lobe of the Pituitary Gland: 3D Turbo Field Echo with Diffusion-Sensitized Driven-Equilibrium Preparation

BACKGROUND AND PURPOSE:3D turbo field echo with diffusion-sensitized driven-equilibrium preparation is a non–echo-planar technique for DWI, which enables high-resolution DWI without field inhomogeneity–related image distortion. The purpose of this study was to evaluate the feasibility of diffusion-sensitized driven-equilibrium turbo field echo in evaluating diffusivity in the normal pituitary gland.MATERIALS AND METHODS:First, validation of diffusion-sensitized driven-equilibrium turbo field echo was attempted by comparing it with echo-planar DWI. Five healthy volunteers were imaged by using diffusion-sensitized driven-equilibrium turbo field echo and echo-planar DWI. The imaging voxel size was 1.5 × 1.5 × 1.5 mm³ for diffusion-sensitized driven-equilibrium turbo field echo and 1.5 × 1.9 × 3.0 mm³ for echo-planar DWI. ADCs measured by the 2 methods in 15 regions of interests (6 in gray matter and 9 in white matter) were compared by using the Pearson correlation coefficient. The ADC in the pituitary anterior lobe was then measured in 10 volunteers by using diffusion-sensitized driven-equilibrium turbo field echo, and the results were compared with those in the pons and vermis by using a paired t test.RESULTS:The ADCs from the 2 methods showed a strong correlation (r = 0.79; P < .0001), confirming the accuracy of the ADC measurement with the diffusion-sensitized driven-equilibrium sequence. The ADCs in the normal pituitary gland were 1.37 ± 0.13 × 10⁻³ mm²/s, which were significantly higher than those in the pons (1.01 ± 0.24 × 10⁻³ mm²/s) and the vermis (0.89 ± 0.25 × 10⁻³ mm²/s, P < .01).CONCLUSIONS:We demonstrated that diffusion-sensitized driven-equilibrium turbo field echo is feasible in assessing ADC in the pituitary gland.

DWI is widely used to diagnose cerebrovascular diseases, intracranial tumors, and inflammation.^1–10 However, it is difficult to evaluate skull base structures by the most common imaging technique used with echo-planar (EP)-DWI. Previous studies have revealed the efficacy of DWI for skull base tumors such as pituitary adenoma; however, they are mostly limited to macroadenomas large enough to calculate the ADC by using EP sequences.^3–7 Compared with EP-DWI, 3D diffusion-sensitized driven-equilibrium turbo field echo (DSDE-TFE) obtained DWI has higher spatial resolution and fewer susceptibility artifacts.¹¹ To our knowledge, to date, the diffusivity of the normal pituitary gland has not been fully evaluated, especially in those glands surrounded by aerated sphenoid sinuses. Therefore, the purpose of this study was to evaluate the feasibility of DSDE-TFE in evaluating diffusivity in the normal pituitary gland.     

Myriad Presentations of Intracranial Meningiomas: Pictoral Essay

Meningiomas are the most common non-glial tumor of the central nervous system (CNS). Seen in middle age with a female preponderance, most of the tumors are solitary and supratentorial with benign histology (WHO grade I). Atypical and anaplastic (malignant) meningiomas (WHO grade II and III), comprise 15–20% of all intracranial meningiomas [1,2,3,4,5]. Magnetic resonance imaging (MRI) is the imaging modality of choice.     

Is Contrast Medium Really Needed for Follow-up MRI of Untreated Intracranial Meningiomas?

BACKGROUND AND PURPOSE:Recent concerns relating to tissue deposition of gadolinium are favoring the use of noncontrast MR imaging whenever possible. The purpose of this study was to assess the necessity of gadolinium contrast for follow-up MR imaging of untreated intracranial meningiomas.MATERIALS AND METHODS:One-hundred twenty-two patients (35 men, 87 women) with meningiomas who underwent brain MR imaging between May 2007 and May 2019 in our institution were included in this retrospective cohort study. We analyzed 132 meningiomas: 73 non-skull base (55%) versus 59 skull base (45%), 93 symptomatic (70%) versus 39 asymptomatic (30%). Fifty-nine meningiomas underwent an operation: 54 World Health Organization grade I (92%) and 5 World Health Organization grade II (8%). All meningiomas were segmented on T1 3D-gadolinium and 2D-T2WI. Agreement between T1 3D-gadolinium and 2D-T2WI segmentations was assessed by the intraclass correlation coefficient.RESULTS:The mean time between MR images was 1485 days (range, 760–3810 days). There was excellent agreement between T1 3D-gadolinium and T2WI segmentations (P < .001): mean tumor volume (T1 3D-gadolinium: 9012.15 [SD, 19,223.03] mm³; T2WI: 8528.45 [SD, 18,368.18 ] mm³; intraclass correlation coefficient = 0.996), surface area (intraclass correlation coefficient = 0.989), surface/volume ratio (intraclass correlation coefficient = 0.924), maximum 3D diameter (intraclass correlation coefficient = 0.986), maximum 2D diameter in the axial (intraclass correlation coefficient = 0.990), coronal (intraclass correlation coefficient = 0.982), and sagittal planes (intraclass correlation coefficient = 0.985), major axis length (intraclass correlation coefficient = 0.989), minor axis length (intraclass correlation coefficient = 0.992), and least axis length (intraclass correlation coefficient = 0.988). Tumor growth also showed good agreement (P < .001), estimated as a mean of 461.87 [SD, 2704.1] mm³/year on T1 3D-gadolinium and 556.64 [SD, 2624.02 ] mm³/year on T2WI.CONCLUSIONS:Our results show excellent agreement between the size and growth of meningiomas derived from T1 3D-gadolinium and 2D-T2WI, suggesting that the use of noncontrast MR imaging may be appropriate for the follow-up of untreated meningiomas, which would be cost-effective and avert risks associated with contrast media.

Recent concerns regarding gadolinium (Gd) compounds are fueling a trend to use contrast media in MR imaging less frequently. Notwithstanding the well-established safety profile of Gd compounds, a small number of immediate adverse effects, which may be life-threatening, has been reported^1,2 at a rate of approximately 0.3%.² Furthermore, repeat administration of Gd-based contrast may lead to deposition of Gd in the dentate nucleus and the globus pallidus,^3-7 which seems to be the case with linear rather than macrocyclic Gd compounds,⁴ despite a normal renal function⁷ and an intact blood-brain barrier.⁶ Health care costs should also be considered because they are a heavy burden to modern Western societies,^8-10 and medical imaging accounts for a large proportion of these costs.¹⁰ Gd-based contrast media significantly contribute to the cost of an MR image, due to the price of the contrast medium itself and also because of the prolonged image-acquisition time. Using contrast media more sparingly could, therefore, reduce these costs considerably.The above-mentioned concerns are particularly pertinent to young patients with incidental or asymptomatic meningiomas in which frequent and long-term follow-up MR imaging is usually performed, the current standard-of-care being MR with Gd-based contrast media.¹¹ Intracranial meningiomas are, by and large, benign World Health Organization (WHO) grade I tumors derived from meningothelial cells,^12,13 representing approximately one-third of all primary central nervous system tumors¹⁴ and 15% of symptomatic intracranial masses.¹⁵ They are extra-axial lesions that usually exhibit slow growth (approximately 14%/year for WHO grade I lesions).¹⁶ However, the growth rate can be substantially higher, particularly in WHO grade II and III meningiomas, necessitating frequent MR imaging follow-up. For instance, the European Association of Neuro-Oncology advocates diligent radiologic follow-up of meningiomas. For small asymptomatic meningiomas, the recommendation of this institution is to assess the tumor dynamics with contrast MR imaging at 6 months after the initial diagnosis and then annually as long as the patient remains asymptomatic.¹¹Quantitative MR imaging parameters such as tumor volume¹⁷ are important in predicting tumor growth and behavior. Nakasu and Nakasu,¹⁸ in 2020, identified large tumor size and annual volume change of ≥2.1 cm³ as the strongest predictors of symptomatic tumor progression. Several other parameters may be important in predicting the potential for rapid tumor growth, such as male sex,¹⁸ younger age,¹⁸ absence of calcification,^18-23 peritumoral edema,^21,22,24 and hyperintensity on T2WI.^{18,19,22,25,26}Considering these points, the purpose of this retrospective cohort study was to assess the hypothesis that size and growth of untreated intracranial meningiomas derived from T1 3D-Gd and 2D-T2WI sequences show good agreement, which would, should this be the case, question the added value of Gd-based contrast media for routine follow-up MRIs of intracranial meningiomas.     

Noninvasive Assessment of IDH Mutational Status in World Health Organization Grade II and III Astrocytomas Using DWI and DSC-PWI Combined with Conventional MR Imaging

BACKGROUND AND PURPOSE:Isocitrate dehydrogenase (IDH) has been shown to have both diagnostic and prognostic implications in gliomas. The purpose of this study was to examine whether DWI and DSC-PWI combined with conventional MR imaging could noninvasively predict IDH mutational status in World Health Organization grade II and III astrocytomas.MATERIALS AND METHODS:We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging in 42 patients with World Health Organization grade II and III astrocytomas. Minimum ADC, relative ADC, and relative maximum CBV values were compared between IDH-mutant and wild-type tumors by using the Mann-Whitney U test. Receiver operating characteristic curve and logistic regression were used to assess their diagnostic performances.RESULTS:Minimum ADC and relative ADC were significantly higher in IDH-mutated grade II and III astrocytomas than in IDH wild-type tumors (P < .05). Minimum ADC with the cutoff value of ≥1.01 × 10⁻³ mm²/s could differentiate the mutational status with a sensitivity, specificity, positive predictive value, and negative predictive value of 76.9%, 82.6%, 91.2%, and 60.5%, respectively. The threshold value of <2.35 for relative maximum CBV in the prediction of IDH mutation provided a sensitivity, specificity, positive predictive value, and negative predictive value of 100.0%, 60.9%, 85.6%, and 100.0%, respectively. A combination of DWI, DSC-PWI, and conventional MR imaging for the identification of IDH mutations resulted in a sensitivity, specificity, positive predictive value, and negative predictive value of 92.3%, 91.3%, 96.1%, and 83.6%.CONCLUSIONS:A combination of conventional MR imaging, DWI, and DSC-PWI techniques produces a high sensitivity, specificity, positive predictive value, and negative predictive value for predicting IDH mutations in grade II and III astrocytomas. The strategy of using advanced, semiquantitative MR imaging techniques may provide an important, noninvasive, surrogate marker that should be studied further in larger, prospective trials.

Infiltrating astrocytomas are the most common primary central nervous system tumors, ranging variably from grade II to IV according to the 2007 World Health Organization classification system.^1,2 Glioma grading is based on histopathologic analysis of tumor differentiation, mitotic activity, cellularity, nuclear atypia, and the extent of microvascular proliferation and may result in a great deal of interobserver variability.^1–3 Therefore, quantitative molecular analyses have the potential to reduce subjectivity and improve diagnosis, prognostication, risk stratification, and management plans. Notably, in the 2016 World Health Organization (WHO) classification, grade II and III astrocytomas are molecularly divided into isocitrate dehydrogenase (IDH) mutant, IDH wild type, and not otherwise specified categories, emphasizing the value of IDH mutation status in astrocytomas.⁴IDH gene mutations, originally discovered in high-grade gliomas in 2008, exist in 60%–90% of grade II and III astrocytomas.^5,6 The IDH gene (including IDH1 and IDH2 genes) plays prominent roles in the metabolism, pathogenesis, and progression of astrocytomas.^7–9 In addition, stratification of grade II and III gliomas into subsets defined by IDH mutation would help identify subgroups with distinct prognostic characteristics, therapeutic response, and clinical management.^10–16 In a study with a cohort of 475 patients, comparison of overall survival between those with WHO grade II and III IDH-mutated astrocytomas showed no remarkable difference, whereas the patients with IDH-mutated tumors survived much longer than those with IDH wild-type tumors.¹⁰ Patients with grade II astrocytomas without IDH mutation were shown to have a poorer prognosis with a 5-year progression-free survival and overall survival rate of 14% and 51%, respectively, compared with 42% and 93% for those with IDH-mutant tumors (P < .001).¹⁷ Moreover, patients with gliomas whose lesions had IDH mutations were more sensitive to chemoradiation therapy and survived longer than those with wild-type IDH.^10,15Currently, immunohistochemical staining and DNA sequencing are the most common methods for determining the IDH mutational status in gliomas. IDH gene mutations may reflect alterations in metabolism, cellularity, and angiogenesis, which may manifest characteristic features on DWI and DSC-PWI.^8,18 DWI can noninvasively provide direct insight into the microscopic physical properties of tissues through observing the Brownian movement of water and reflecting cellularity within the lesions by ADC values.^19–21 In vivo measurement of relative CBV (rCBV) has been demonstrated to correlate with tumor vascularity.^22–24 ADC values derived from DWI and DSC-PWI have been used to detect IDH gene status in gliomas in recent research.^24–26 Meanwhile, conventional MR imaging (cMRI) was also used to assess other characteristics of gliomas (eg, location, distinctness of borders, enhancement, and edema).^17,27,28To our knowledge, there is no study in the literature combining cMRI with diffusion and perfusion techniques to distinguish IDH genotypes. The purpose of this study was to explore whether a novel approach, in which DWI and DSC-PWI were combined with cMRI, was able to noninvasively predict IDH mutational status in WHO grade II and III astrocytomas.     

Predictive Models in Differentiating Vertebral Lesions Using Multiparametric MRI

BACKGROUND AND PURPOSE:Conventional MR imaging has high sensitivity but limited specificity in differentiating various vertebral lesions. We aimed to assess the ability of multiparametric MR imaging in differentiating spinal vertebral lesions and to develop statistical models for predicting the probability of malignant vertebral lesions.MATERIALS AND METHODS:One hundred twenty-six consecutive patients underwent multiparametric MRI (conventional MR imaging, diffusion-weighted MR imaging, and in-phase/opposed-phase imaging) for vertebral lesions. Vertebral lesions were divided into 3 subgroups: infectious, noninfectious benign, and malignant. The cutoffs for apparent diffusion coefficient (expressed as 10⁻³ mm²/s) and signal intensity ratio values were calculated, and 3 predictive models were established for differentiating these subgroups.RESULTS:Of the lesions of the 126 patients, 62 were infectious, 22 were noninfectious benign, and 42 were malignant. The mean ADC was 1.23 ± 0.16 for infectious, 1.41 ± 0.31 for noninfectious benign, and 1.01 ± 0.22 mm²/s for malignant lesions. The mean signal intensity ratio was 0.80 ± 0.13 for infectious, 0.75 ± 0.19 for noninfectious benign, and 0.98 ± 0.11 for the malignant group. The combination of ADC and signal intensity ratio showed strong discriminatory ability to differentiate lesion type. We found an area under the curve of 0.92 for the predictive model in differentiating infectious from malignant lesions and an area under the curve of 0.91 for the predictive model in differentiating noninfectious benign from malignant lesions. On the basis of the mean ADC and signal intensity ratio, we established automated statistical models that would be helpful in differentiating vertebral lesions.CONCLUSIONS:Our study shows that multiparametric MRI differentiates various vertebral lesions, and we established prediction models for the same.

MR imaging is the preferred technique in the diagnostic work-up of benign and malignant vertebral lesions. Morphologic criteria alone could not differentiate benign and malignant spinal lesions in 6%–21% of cases.^1–3 Due to the limited specificity of conventional MR imaging,⁴ radiologists often have trouble differentiating common spinal pathologies such as osteoporotic vertebral collapse, infectious spondylodiscitis, and metastasis. Recently, multiparametric MR imaging (mpMRI) has shown the ability to localize, detect, and stage various diseases.^5–8 The mpMRI approach combines anatomic sequences (T1- and T2-weighted MR imaging) with functional imaging sequences. Functional and quantitative MR imaging methods, such as DWI, dynamic contrast-enhanced MR imaging, and in-phase/opposed-phase imaging, measure the Brownian motion of water molecules, regional vascular properties of the tumor, and fat quantification, respectively.^6–9DWI has been used in the differentiation of benign and malignant spinal lesions.^10–12 Signal characteristics of vertebral lesions were evaluated on DWI for qualitative assessment, and the ADC was calculated for quantitative analysis. In general, malignant lesions yield lower ADC compared with noninfectious benign and infectious lesions due to increased cellularity and decreased extracellular space in malignant lesions.^10–12 In-phase/opposed-phase MR imaging quantifies fat in tissues and has been used in lesions of the adrenal gland and liver.^13–17 It has also been used in diagnostic work-up of spinal lesions, and the results demonstrated a significant difference in the signal intensity ratio (SIR) between benign and malignant vertebral lesions.^9,18–21The hypothesis for this study was that the mpMRI approach would increase the discriminatory ability of different vertebral lesions. The aim of the present study was to evaluate the ability of mpMRI in differentiating vertebral lesions and to establish statistical models for predicting the probability of malignant (GPM) lesions compared with noninfectious benign (GPN) and infectious (GPI) ones. The cutoffs of the ADC and SIR values were obtained to differentiate GPM lesions from GPI and GPN lesions. Furthermore, we considered GPI and GPN as all benign compared with the malignant lesions. The cutoff values of the ADC and SIR for differentiating malignant from all benign lesions were also obtained.Although attempts have been made to assess the role of quantitative DWI or in-phase/opposed-phase imaging in differentiating vertebral lesions, to the best of our knowledge, no previous study has evaluated the ability of mpMRI to differentiate malignant or infectious lesions from noninfectious benign lesions.     

Relationship between Shear Stiffness Measured by MR Elastography and Perfusion Metrics Measured by Perfusion CT of Meningiomas

BACKGROUND AND PURPOSE:When managing meningiomas, intraoperative tumor consistency and histologic subtype are indispensable factors influencing operative strategy. The purposes of this study were the following: 1) to investigate the correlation between stiffness assessed with MR elastography and perfusion metrics from perfusion CT, 2) to evaluate whether MR elastography and perfusion CT could predict intraoperative tumor consistency, and 3) to explore the predictive value of stiffness and perfusion metrics in distinguishing among histologic subtypes of meningioma.MATERIALS AND METHODS:Mean tumor stiffness and relative perfusion metrics (blood flow, blood volume, and MTT) were calculated (relative to normal brain tissue) for 14 patients with meningiomas who underwent MR elastography and perfusion CT before surgery (cohort 1). Intraoperative tumor consistency was graded by a neurosurgeon in 18 patients (cohort 2, comprising the 14 patients from cohort 1 plus 4 additional patients). The correlation between tumor stiffness and perfusion metrics was evaluated in cohort 1, as was the ability of perfusion metrics to predict intraoperative tumor consistency and discriminate histologic subtypes. Cohort 2 was analyzed for the ability of stiffness to determine intraoperative tumor consistency and histologic subtypes.RESULTS:The relative MTT was inversely correlated with stiffness (P = .006). Tumor stiffness was positively correlated with intraoperative tumor consistency (P = .01), while perfusion metrics were not. Relative MTT significantly discriminated transitional meningioma from meningothelial meningioma (P = .04), while stiffness did not significantly differentiate any histologic subtypes.CONCLUSIONS:In meningioma, tumor stiffness may be useful to predict intraoperative tumor consistency, while relative MTT may potentially correlate with tumor stiffness and differentiate transitional meningioma from meningothelial meningioma.

Meningioma is the most common primary intracranial tumor with an incidence of approximately 8 cases per 10,000 persons per year.¹ Radiosurgery, chemotherapy, or arterial embolization play supplementary roles, though surgical resection is the primary treatment for meningiomas. Tumor consistency is recognized as a major indicator of complete resection for meningiomas.² To date, various imaging modalities including T2-weighted images, diffusion MR imaging measurements, and magnetization transfer imaging have been investigated to predict meningioma consistency.³ However, there have been conflicting results, and no widely accepted method has been established.MR elastography (MRE) is a dynamic MR imaging–based technique used for the noninvasive measurement of the mechanical properties of soft tissue in vivo.⁴ Recently, the mechanical properties of the brain have been studied in normal aging,^5-9 Alzheimer disease,^6,10,11 Parkinson disease,¹² frontotemporal dementia,⁶ normal pressure hydrocephalus,⁶ and brain tumors,¹³ including menigniomas.^14-17 More recently, slip interface imaging using specialized processing of MRE data was shown to provide a dynamic measure of adherence between the tumor and the adjacent brain tissue.¹⁸The global shear modulus of soft biologic tissue can be influenced by the scale of perfusion,¹⁹ which relates to the topology and geometry of microvessels,²⁰ indicating a potential effect of perfusion on the macroscopic viscoelastic response of brain tissue. Previous MRE studies have indicated a close correlation between tissue perfusion and mechanical properties in the brain^21,22 and abdominal organs.²³ Moreover, in investigations of the pathologic determinants underpinning MRE data,^24,25 microvascular density, which is related to perfusion metrics,²¹ has been shown to contribute to the stiffness of soft brain tumor models in mice. Nevertheless, the perfusion conditions and mechanical properties of meningiomas have not been concurrently analyzed. Meningioma consistency and histologic subtype are indispensable factors influencing operative strategy and patient counseling. Recently, MRE has been increasingly recognized as a useful indicator of meningioma consistency,^14-17 while perfusion metrics provide physiologic and functional information about the tumor microenvironment. Because stiffness and perfusion status are intricately related, MRE and perfusion metrics may serve to preoperatively characterize the viscoelastic properties of meningiomas and further develop clinically applicable predictors for intraoperative tumor consistency. Relatively few studies have reported the relationship between stiffness ¹⁶ or perfusion metrics ^26-28 and histologic subtype, and no definite association has been established. Investigating the relationship of stiffness and perfusion metrics to intraoperative meningioma consistency and histologic subtypes may contribute to understanding and objective comparison of these techniques and provide valuable information affecting risk assessment, patient management, and workflow optimization.The purposes of this study were the following: 1) to investigate the correlation between stiffness and perfusion metrics, 2) to evaluate whether preoperative MRE and perfusion metrics could predict intraoperative tumor consistency, and 3) to explore the predictive value of stiffness and perfusion metrics in distinguishing among histologic subtypes of meningiomas.     

Evaluating Instantaneous Perfusion Responses of Parotid Glands to Gustatory Stimulation Using High-Temporal-Resolution Echo-Planar Diffusion-Weighted Imaging

BACKGROUND AND PURPOSE:Parotid glands secrete and empty saliva into the oral cavity rapidly after gustatory stimulation. However, the role of the temporal resolution of DWI in investigating parotid gland function remains uncertain. Our aim was to design a high-temporal-resolution echo-planar DWI pulse sequence and to evaluate the instantaneous MR perfusion responses of the parotid glands to gustatory stimulation.MATERIALS AND METHODS:This prospective study enrolled 21 healthy volunteers (M/F = 2:1; mean age, 45.2 ± 12.9 years). All participants underwent echo-planar DWI (total scan time, 304 seconds; temporal resolution, 4 s/scan) on a 1.5T MR imaging scanner. T2WI (b = 0 s/mm²) and DWI (b = 200 s/mm²) were qualitatively assessed. Signal intensity of the parotid glands on T2WI, DWI, and ADC was quantitatively analyzed. One-way ANOVA with post hoc group comparisons with Bonferroni correction was used for statistical analysis. P < .05 was statistically significant.RESULTS:Almost perfect interobserver agreement was achieved (κ ≥ 0.656). The parotid glands had magnetic susceptibility artifacts in 14.3% (3 of 21) of volunteers during swallowing on DWI but were free from perceptible artifacts at the baseline and at the end of scans on all images. Increased ADC and reduced signal intensity of the parotid glands on T2WI and DWI occurred immediately after oral administration of lemon juice. Maximal signal change of ADC (24.8% ± 10.8%) was significantly higher than that of T2WI (−10.1% ± 5.2%, P < .001). The recovery ratio of ADC (100.71% ± 42.34%) was also significantly higher than that of T2WI (22.36% ± 15.54%, P < .001).CONCLUSIONS:Instantaneous parotid perfusion responses to gustatory stimulation can be quantified by ADC by using high-temporal-resolution echo-planar DWI.

Quantification of normal salivary gland function is of paramount clinical importance because it is the foundation of accurately evaluating disease-related salivary gland functional impairment. Salivary gland function can be estimated by several methods such as saliva collection,¹ laboratory measurement of the chemical and biochemical components,² scintigraphy,³ single-photon emission CT,⁴ and positron-emission tomography.⁵ MR imaging is superior to saliva collection and laboratory and biologic studies by providing morphologic and functional information of the parotid glands simultaneously and specifically for individual salivary glands. On the other hand, MR imaging is also superior to scintigraphy, SPECT, and PET because of its high spatial resolution and radiation-free nature.In recent decades, DWI has been increasingly applied to probe salivary gland function in addition to evaluating tumors,^6–11 connective tissue disorders,¹² Sjögren syndrome,^13,14 and postradiotherapy change^15–19 of the parotid glands. However, 2 mutually opposed trends of parotid apparent diffusion coefficient changes after gustatory stimulation have been observed in different study groups, even in healthy volunteers. While some researchers demonstrated an increase of parotid ADC after gustatory stimulation,^{14,16,20–23} others showed a decrease of parotid ADC after this stimulation.^15,24 Such discrepancy has been partially attributed to the different types and dosages of the stimulators.¹⁶ Nevertheless, the discrepancy of diffusional responses to gustatory stimulation in the aforementioned DWI studies has raised concern for whether the normal salivary gland function has been evaluated appropriately with DWI.The role of the temporal resolution of DWI, which might potentially influence researchers in interpreting parotid gland function, has not been documented to date, to our knowledge. Via parasympathetic innervation, salivary glands secrete and empty saliva into the oral cavity rapidly after gustatory stimulation. Current DWI studies might have limitations in catching the instantaneous responses of the parotid glands due to insufficient temporal resolution. We hypothesized that the parotid glands respond to the oral administration of lemon juice on the order of seconds. The aim of our study was to design a high-temporal-resolution echo-planar pulse sequence for DWI and to quantify the instantaneous MR perfusion responses of the parotid glands to gustatory stimulation.     

The added value of apparent diffusion coefficient to cerebral blood volume in the preoperative grading of diffuse gliomas

BACKGROUND AND PURPOSE:In cerebral gliomas, rCBV correlates with tumor grade and histologic findings of vascular proliferation. Moreover, ADC assesses water diffusivity and is inversely correlated with tumor grade. In the present work, we have studied whether combined rCBV and ADC values improve the diagnostic accuracy of MR imaging in the preoperative grading of gliomas.MATERIALS AND METHODS:One hundred sixty-two patients with histopathologically confirmed diffuse gliomas underwent DWI and DSC. Mean rCBV and ADC values were compared among the tumor groups with the Student t test or ANOVA. ROC analysis was used to determine rCBV and ADC threshold values for glioma grading.RESULTS:rCBV had significantly different values between grade II and IV gliomas and between grade III and IV tumors, but there were no significant differences between grade II and III gliomas (P > .05). Grade II and III tumors also did not differ when astrocytomas, oligodendrogliomas, and oligoastrocytomas were considered separately. ADC values were significantly different for all 3 grades. The ADC threshold value of 1.185 × 10⁻³ mm²/s and the rCBV cutoff value of 1.74 could be used with high sensitivity in the characterization of high-grade gliomas. The area under the ROC curve for the maximum rCBV and minimum ADC was 0.72 and 0.75, respectively. The combination of rCBV and ADC values increased the area under the ROC curve to 0.83.CONCLUSIONS:ADC measurements are better than rCBV values for distinguishing the grades of gliomas. The combination of minimum ADC and maximum rCBV improves the diagnostic accuracy of glioma grading.

Gliomas are the most common primary neoplasms of the brain in adults,^1,2 ranging in grade from low to high. Glioma grading is based on the histopathologic assessment of the tumor and is critical for planning therapeutic approaches and assessing prognosis and response to therapy.² Advanced MR imaging techniques such as DSC and DWI provide physiologic information that complements the anatomic information obtained from conventional MR imaging.^3–6 DWI quantifies cellularity on the basis of the premise that water diffusivity within the extracellular compartment is inversely related to the content and attenuation of the intracellular space.⁷ The higher the tumor cellularity and grade are, the lower the ADC is because of decreased water diffusivity.^6–8 However, other factors may be complicating this relationship: ADC increases with increased edema and increased edema is seen in high-grade tumors. DSC provides noninvasive assessment of tumor vascularity and angiogenesis^3–6,9 through the examination of the degradation of signal intensity with time associated with the first pass of a bolus of paramagnetic contrast agent.⁹ Because higher vascularity corresponds to a higher tumor grade, as the grade of the astrocytoma increases, the maximum tumor CBV tends to increase.^3,6,7The aim of this study was to evaluate the diagnostic accuracy of combined ADC and CBV values in the preoperative differentiation of diffuse gliomas. Our objectives were the following: 1) to calculate CBV and ADC values for diffuse gliomas included in the study, 2) to establish whether there is any difference in rCBV and ADC values in gliomas classified by tumor grade and histology, 3) to estimate a cutoff CBV and ADC value for differentiation of high- and low-grade gliomas, and 4) to investigate whether combined CBV and ADC values improve the diagnostic accuracy of MR imaging.     

A Prognostic Model Based on Preoperative MRI Predicts Overall Survival in Patients with Diffuse Gliomas

BACKGROUND AND PURPOSE:Diffuse gliomas are classified as grades II–IV on the basis of histologic features, with prognosis determined mainly by clinical factors and histologic grade supported by molecular markers. Our aim was to evaluate, in patients with diffuse gliomas, the relationship of relative CBV and ADC values to overall survival. In addition, we also propose a prognostic model based on preoperative MR imaging findings that predicts survival independent of histopathology.MATERIALS AND METHODS:We conducted a retrospective analysis of the preoperative diffusion and perfusion MR imaging in 126 histologically confirmed diffuse gliomas. Median relative CBV and ADC values were selected for quantitative analysis. Survival univariate analysis was made by constructing survival curves by using the Kaplan-Meier method and comparing subgroups by log-rank probability tests. A Cox regression model was made for multivariate analysis.RESULTS:The study included 126 diffuse gliomas (median follow-up of 14.5 months). ADC and relative CBV values had a significant influence on overall survival. Median overall survival for patients with ADC < 0.799 × 10⁻³ mm²/s was <1 year. Multivariate analysis revealed that patient age, relative CBV, and ADC values were associated with survival independent of pathology. The preoperative model provides greater ability to predict survival than that obtained by histologic grade alone.CONCLUSIONS:ADC values had a better correlation with overall survival than relative CBV values. A preoperative prognostic model based on patient age, relative CBV, and ADC values predicted overall survival of patients with diffuse gliomas independent of pathology. This preoperative model provides a more accurate predictor of survival than histologic grade alone.

Diffuse gliomas are the second most common primary CNS neoplasms, behind meningiomas, and account for roughly 80% of primary malignant brain tumors.^1–3Diffuse gliomas are a heterogeneous group of neoplasms classified according to the World Health Organization system as grades II–IV on the basis of histologic features, including cell density nuclear atypia, mitotic activity, endothelial proliferation, and necrosis.^3,4 The prognosis for these tumors is determined mainly by histologic grade,³ with a median survival of approximately 3 years for anaplastic astrocytoma and 1 year for glioblastoma.⁵ However, it has been shown that histologic classification of gliomas remains insufficient due to its lack of precision in terms of prognosis.⁶ This classification for phenotype determination and grade is also subjective due to the fact that 1 histologic subtype could comprise different molecular subtypes with different prognoses.⁶ In recent years, extensive molecular studies⁷ have identified diagnostic and prognostic markers in gliomas that support the World Health Organization histologic classification.⁴ 1p19q codeletion, methylation of the O⁶-methylguanine DNA methyltransferase gene promoter, and isocitrate dehydrogenases 1 and 2 gene mutations are the 3 most important markers in diffuse gliomas and may influence the sensitivity of these tumors to treatment.⁴The role of neuroimaging has been widely studied in the literature, not only in the preoperative grading of diffuse gliomas⁸ but also in the determination of tumor response to treatment or tumor progression.⁹ However, the results about the utility of imaging techniques have been mixed, especially those in diffusion and perfusion MR imaging, in the determination of the prognosis of diffuse gliomas. The purposes of our study were as follows: 1) to evaluate the relationship of relative cerebral blood volume (rCBV) and ADC values to overall survival in a group of patients with histologically confirmed diffuse gliomas, and 2) to establish a prognostic model based on preoperative MR imaging findings that could predict overall survival regardless of histology.     

Preoperative Embolization of Intracranial Meningiomas: Efficacy,Technical Considerations,and Complications

BACKGROUND AND PURPOSE:Preoperative embolization for intracranial meningiomas offers potential advantages for safer and more effective surgery. However, this treatment strategy has not been examined in a large comparative series. The purpose of this study was to review our experience using preoperative embolization to understand the efficacy, technical considerations and complications of this technique.MATERIALS AND METHODS:We performed a retrospective review of patients undergoing intracranial meningioma resection at our institution (March 2001 to December 2012). Comparisons were made between embolized and nonembolized patients, including patient and tumor characteristics, embolization method, operative blood loss, complications, and extent of resection. Logistic regression analyses were used to identify factors predictive of operative blood loss and extent of resection.RESULTS:Preoperatively, 224 patients were referred for embolization, of which 177 received embolization. No complications were seen in 97.1%. There were no significant differences in operative duration, extent of resection, or complications. Estimated blood loss was higher in the embolized group (410 versus 315 mL, P = .0074), but history of embolization was not a predictor of blood loss in multivariate analysis. Independent predictors of blood loss included decreasing degree of tumor embolization (P = .037), skull base location (P = .005), and male sex (P = .034). Embolization was not an independent predictor of gross total resection.CONCLUSIONS:Preoperative embolization is a safe option for selected meningiomas. In our series, embolization did not alter the operative duration, complications, or degree of resection, but the degree of embolization was an independent predictor of decreased operative blood loss.

Preoperative embolization has been an option for adjunctive treatment of intracranial meningiomas for almost 4 decades, but it remains used in only a minority of cases.¹ Meningiomas are commonly supplied by the middle meningeal, accessory meningeal, ascending pharyngeal, or occipital branches of the external carotid artery (ECA), which are easily accessible by selective microcatheterization.² Branches of the internal carotid artery and pial feeders supplying the tumor may also be embolized,^3–6 though these vessels are typically more difficult to access and are associated with a higher risk of parenchymal infarct. In an attempt to change the tumor characteristics to increase the likelihood of a gross total resection and minimize operative morbidity, a variety of embolization materials have been used, including polyvinyl alcohol (PVA) particles,^7,8 large-caliber microspheres,^8,9 ethylene-vinyl alcohol (Onyx; Covidien, Irvine, California),^10,11 detachable coils,¹² fibrin glue¹³ and hyperosmolar mannitol.¹⁴ The potential advantages of preoperative embolization include decreased operative duration, reduced operative blood loss, and alteration of tumor consistency, all of which decrease the technical difficulty of surgical resection and increase the likelihood of achieving a more complete resection. Embolization likely causes histopathologic changes within the meningioma, including necrosis, ischemic changes, and microvascular fibrinoid changes.¹⁵ Hypoxia caused by disruption of tumoral blood supply also causes changes in protein expression consistent with angiogenesis and promotion of growth,¹⁶ along with cytologic changes, including infiltration of macrophages.¹⁷ The combination of these changes may make histologic examination of embolized meningiomas more difficult because they may histopathologically resemble higher grade tumors.^15,18–20 Embolization also carries with it the risk of procedural complications, including large-vessel dissection, microcatheter fracture, and unintended arterial or venous occlusion resulting in hemorrhagic or ischemic infarct.^1,7,21–28Series of meningiomas that were preoperatively embolized have been recently published,⁷ but the operative findings and postoperative course for embolized tumors have not been compared with nonembolized tumors in a large modern series. In this study, we sought to review our outcomes following preoperative angiography, embolization when possible, and resection of intracranial meningiomas for the following objectives: 1) to assess the effect of preoperative embolization on operative time, surgical blood loss, and extent of resection; 2) to compare outcomes and complications between resection of embolized and nonembolized meningiomas; and 3) to determine predictors of objective utility of meningioma embolization.     

Quantitative Diffusion-Weighted MRI Parameters and Human Papillomavirus Status in Oropharyngeal Squamous Cell Carcinoma

BACKGROUND AND PURPOSE:Patients with human papillomavirus–positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus–negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC may also provide prognostic information. We explored whether human papillomavirus status and ADC values are independent tumor characteristics.MATERIALS AND METHODS:Forty-four patients with oropharyngeal squamous cell carcinomas underwent pretreatment DWI. ADC values for the primary tumors were determined by using 3 b-values in an ROI containing the largest area of solid tumor on a single section of an axial DWI image. Human papillomavirus status was determined with p16 immunostaining, followed by high-risk human papillomavirus DNA detection on the p16-positive cases.RESULTS:Twenty-two patients were human papillomavirus–positive (50.0%). ADC values were not significantly different between human papillomavirus–negative (ADC_mean = 1.56 [1.18–2.18] × 10³ mm²/s) and human papillomavirus–positive tumors (ADC_mean = 1.46 [1.07–2.16] × 10³ mm²/s).CONCLUSIONS:No significant association between ADC and human papillomavirus status was found in oropharyngeal squamous cell carcinomas. In our study population, differences in genetic and histologic features between human papillomavirus–positive and human papillomavirus–negative oropharyngeal squamous cell carcinomas did not translate into different ADC values. Long-term follow-up studies are needed to establish whether ADC has prognostic value and whether this is independent of the human papillomavirus status.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide.¹ During the past decades, it has been well-established that besides tobacco smoking and alcohol consumption, human papillomavirus (HPV) is an important etiologic factor in the development of HNSCC, in particular squamous cell carcinomas in the oropharynx (OPSCC). HPV-positive and HPV-negative OPSCCs are different disease entities.² Patients with HPV-positive OPSCC show higher response rates to treatment and have a better overall survival compared with those with HPV-negative OPSCC, despite the more often regionally advanced disease presentation in patients with HPV-positive OPSCC.^3,4 In addition, the genetic route to cancer is different for HPV-positive OPSCC,^5,6 and HPV-related tumors have distinct histologic features.^7,8 In this context, traditional prognostic factors such as tumor size and lymph node invasion may be insufficient to fully classify patients into risk groups. Identification of other prognostic tumor characteristics may lead to an improved patient selection and, as a result, higher responses to treatment and probably less treatment-induced morbidity.DWI is a noninvasive functional technique that characterizes tissue on the basis of the random motion of water molecules, which is mainly influenced by the volume of extracellular space and the presence of cell membranes. Differences in water mobility can be quantified with the ADC: Hypocellular or necrotic tissue or both are characterized by a high ADC, whereas hypercellular tissue is characterized by a low ADC. Hence, parameters from DWI, such as ADC, could indicate biologic dissimilarities among tumors. Furthermore, studies in breast cancer have demonstrated that the ADC value significantly correlates with the expression of specific biologic markers of disease, such as estrogen receptor and progesterone receptor.^9,10 ADC is a possible prognostic factor in HNSCC; several studies have shown that HNSCC with relatively low pretreatment ADC values responds better to chemoradiotherapy than tumors with higher pretreatment ADC values.^11–14 Additionally, HPV-positive OPSCC often has a different histology from HPV-negative OPSCC, characterized by ovoid-to-spindle-shaped hyperchromatic cells without keratinization and without a stromal response,¹⁵ and it can by hypothesized that these histologic characteristics translate into low pretreatment ADC values; if so, this hypothesis would support the general notion that low ADC correlates with a better response to chemoradiotherapy. Limited information is available on the relation between HPV involvement and ADC values.¹⁶In this study, we investigated the possible association between ADC values derived from DWI and the presence of biologically active HPV in patients with OPSCC.     

Assessment of Angiographic Vascularity of Meningiomas with Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted Imaging and Diffusion Tensor Imaging

BACKGROUND AND PURPOSE:The roles of DTI and dynamic susceptibility contrast-enhanced–PWI in predicting the angiographic vascularity of meningiomas have not been studied. We aimed to investigate if these 2 techniques could reflect the angiographic vascularity of meningiomas.MATERIALS AND METHODS:Thirty-two consecutive patients with meningiomas who had preoperative dynamic susceptibility contrast-enhanced–PWI, DTI, and conventional angiography were retrospectively included. The correlations between angiographic vascularity of meningiomas, classified with a 4-point grading scale, and the clinical or imaging variables—age and sex of patient, as well as size, CBV, fractional anisotropy, and ADC of meningiomas—were analyzed. The meningiomas were dichotomized into high-vascularity and low-vascularity groups. The differences in clinical and imaging variables between the 2 groups were compared. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of these variables.RESULTS:In meningiomas, angiographic vascularity correlated positively with CBV but negatively with fractional anisotropy. High-vascularity meningiomas demonstrated significantly higher CBV but lower fractional anisotropy as compared with low-vascularity meningiomas. In differentiating between the 2 groups, the area under the curve values were 0.991 for CBV and 0.934 for fractional anisotropy on receiver operating characteristic curve analysis.CONCLUSIONS:CBV and fractional anisotropy correlate well with angiographic vascularity of meningiomas. They may differentiate between low-vascularity and high-vascularity meningiomas.

Meningiomas account for approximately one-third of primary brain tumors.¹ Preoperative evaluation of meningioma with conventional angiography, the reference standard for tumor vasculature assessment, may help in surgical planning by providing important information such as tumor vascularity, vascular anatomy of feeding arteries, and draining veins. However, cerebral conventional angiography is invasive and not without risk. A previous study reported that there were 1.3% neurologic complications, among which 0.5% were permanent.²Several MR imaging techniques have been shown to be able to provide some of the vascular information of meningiomas that could only be obtained with conventional angiography in the past. Arterial spin-labeling and regional perfusion imaging techniques could determine if the vascular supply of a meningioma was from the external carotid artery, the ICA, or both.³ MRA, on the other hand, helped to identify the arterial branches primarily supplying the meningiomas.⁴ To our knowledge, there is no report on the use of quantitative MR techniques to predict the degree of angiographic vascularity of meningiomas.In contrast to conventional MR imaging, which provides only structural information, advanced MR techniques such as dynamic susceptibility contrast-enhanced PWI and DTI may provide physiologic information that helps in lesion characterization. The attenuation of T2-weighted signal measured with DTI after 2 extra gradient pulses can be linked to water diffusivity. Fractional anisotropy (FA) and ADC are quantitative metrics derived from DTI for water diffusivity measurement.⁵ DSC-PWI, on the other hand, measures T2*-weighted signal intensity loss that occurs dynamically over bolus injection of contrast medium, from which relative CBV, a quantitative marker of tumor angiogenesis, can be computed.⁶Both DTI^7,8 and DSC-PWI^9–11 had been reported to be useful in subtyping meningiomas. The microvessel area of meningiomas determined by histopathology was found to correlate with relative CBV derived from DSC-PWI.¹¹ In the present study, we aimed to investigate if DTI and DSC-PWI could reflect the angiographic vascularity of meningiomas. To our knowledge, the roles of DTI and DSC-PWI in assessing the angiographic vascularity of meningiomas have never been studied.     

Acute Cytotoxic and Vasogenic Edema after Subarachnoid Hemorrhage: A Quantitative MRI Study

BACKGROUND AND PURPOSE:The mechanism of early brain injury following subarachnoid hemorrhage is not well understood. We aimed to evaluate if cytotoxic and vasogenic edema are contributing factors.MATERIALS AND METHODS:A retrospective analysis was conducted in patients with SAH undergoing diffusion-weighted MR imaging within 72 hours of onset. Apparent diffusion coefficient values derived from DWI were evaluated by using whole-brain histograms and 19 prespecified ROIs in patients with SAH and controls with normal findings on MRI. Cytotoxic edema observed outside the ROIs was assessed in patients with SAH. The average median ADC values were compared between patients with SAH and controls and patients with SAH with mild (Hunt and Hess 1–3) versus severe early brain injury (Hunt and Hess 4–5).RESULTS:We enrolled 33 patients with SAH and 66 controls. The overall average median whole-brain ADC was greater for patients with SAH (808 × 10⁻⁶ mm²/s) compared with controls (788 × 10⁻⁶ mm²/s, P < .001) and was higher in patients with SAH across ROIs after adjusting for age: cerebral gray matter (826 versus 803 × 10⁻⁶ mm²/s, P = .059), cerebral white matter (793 versus 758 × 10⁻⁶ mm²/s, P = .023), white matter tracts (797 versus 739 × 10⁻⁶ mm²/s, P < .001), and deep gray matter (754 versus 713 × 10⁻⁶ mm²/s, P = .016). ADC values trended higher in patients with Hunt and Hess 4–5 versus those with Hunt and Hess 1–3. Early cytotoxic edema was observed in 13 (39%) patients with SAH and was more prevalent in those with severe early brain injury (87.5% of patients with Hunt and Hess 4–5 versus 24.0% of those with Hunt and Hess 1–3, P = .001).CONCLUSIONS:Age-adjusted ADC values were globally increased in patients with SAH compared with controls, even in normal-appearing brain regions, suggesting diffuse vasogenic edema. Cytotoxic edema was also present in patients with SAH and correlated with more severe early brain injury.

Early brain injury (EBI) incurred during aneurysm rupture in spontaneous subarachnoid hemorrhage is a major predictor of poor functional outcome,^1,2 yet the mechanism for EBI is not well-understood. In both animal and human models, SAH leads to transiently elevated intracranial pressure with concomitant inadequate cerebral blood flow and, in severe cases, intracranial circulatory arrest.^3,4 This transient global hypoperfusion is associated with endothelial activation, microthrombosis, ischemia, and vasogenic edema in animal models.^5–7 As a part of routine clinical MR imaging at many institutions, diffusion-weighted imaging presents a unique opportunity for the study of patients with SAH in the acute period. Apparent diffusion coefficient values may serve as a practical and useful biomarker for the severity of EBI following SAH. In humans, we and others have demonstrated that MR imaging–detected infarctions on DWI occur acutely after SAH and before the onset of delayed cerebral ischemia/vasospasm.^8–11These infarctions are more common in patients with more severe EBI (Hunt and Hess [HH] 4–5); occur in unusual, nonvascular patterns (eg, corpus callosum, bilateral medial frontal lobes); and are associated with an increased risk of delayed cerebral ischemia and worse 3-month functional outcomes.^8–10 The volume of infarction associated with worse functional outcomes is small, however.⁸ Thus, this finding led us to hypothesize that conventional, nonquantitative MR imaging techniques are not sensitive enough to detect the full extent of brain injury.We hypothesized that patients with SAH (compared with controls) would demonstrate global reductions in apparent diffusion coefficient values, indicating diffuse cytotoxic edema presumably due to ischemia/hypoperfusion, when whole-brain ADC mapping and ROI quantitative analyses were applied. We further hypothesized that patients with SAH with evidence of severe EBI would have a greater burden of cytotoxic edema than those with mild EBI.     

Diffusion and Perfusion MRI Findings of the Signal-Intensity Abnormalities of Brain Associated with Developmental Venous Anomaly

BACKGROUND AND PURPOSE:Developmental venous anomalies are the most common intracranial vascular malformation. Increased signal-intensity on T2-FLAIR images in the areas drained by developmental venous anomalies are encountered occasionally on brain imaging studies. We evaluated diffusion and perfusion MR imaging findings of the abnormally high signal intensity associated with developmental venous anomalies to describe their pathophysiologic nature.MATERIALS AND METHODS:We retrospectively reviewed imaging findings of 34 subjects with signal-intensity abnormalities associated with developmental venous anomalies. All subjects underwent brain MR imaging with contrast and diffusion and perfusion MR imaging. Regions of interest were placed covering abnormally high signal intensity around developmental venous anomalies on fluid-attenuated inversion recovery imaging, and the same ROIs were drawn on the corresponding sections of the diffusion and perfusion MR imaging. We measured the apparent diffusion coefficient, relative cerebral blood volume, relative mean transit time, and time-to-peak of the signal-intensity abnormalities around developmental venous anomalies and compared them with the contralateral normal white matter. The Mann-Whitney U test was used for statistical analysis.RESULTS:The means of ADC, relative cerebral blood volume, relative mean transit time, and TTP of signal-intensity abnormalities around developmental venous anomalies were calculated as follows: 0.98 ± 0.13 10⁻³mm²/s, 195.67 ± 102.18 mL/100 g, 16.74 ± 7.38 seconds, and 11.65 ± 7.49 seconds, respectively. The values of normal WM were as follows: 0.74 ± 0.08 10⁻³mm²/s for ADC, 48.53 ± 22.85 mL/100 g for relative cerebral blood volume, 12.12 ± 4.27 seconds for relative mean transit time, and 8.35 ± 3.89 seconds for TTP. All values of ADC, relative cerebral blood volume, relative mean transit time, and TTP in the signal-intensity abnormalities around developmental venous anomalies were statistically higher than those of normal WM (All P < .001, respectively).CONCLUSIONS:The diffusion and perfusion MR imaging findings of the signal-intensity abnormalities associated with developmental venous anomaly suggest that the nature of the lesion is vasogenic edema with congestion and delayed perfusion.

Developmental venous anomalies (DVAs) are encountered frequently on brain imaging studies. DVAs are identified in up to 2% of the general population, and they are the most common intracranial vascular malformation (63% and 50% of all malformations in postmortem examinations and MR imaging series, respectively).^1,2 They are composed of dilated medullary veins that drain centripetally and radially into enlarged transcortical or subependymal collector veins.^3–5 DVAs serve as normal drainage routes of the brain tissue because the normal venous drainage pattern is underdeveloped in the area adjacent to the DVA. These venous channels have no malformed or neoplastic elements and are generally described as having normal intervening parenchyma.^6,7 However, increased signal intensity (SI) on T2 FLAIR images in the areas drained by DVAs have been reported in 7.8%–54.1% of MR imaging investigations.^8–10 Such abnormal SI related to DVAs has been explained as edema, ischemia, demyelination, gliosis, leukoaraiosis, or a combination of these conditions.^11,12 Several studies have been undertaken to understand the mechanism of SI change.^13–15 However, there has been no report of the diffusion and perfusion changes of abnormal SI in the area of DVAs by using diffusion- and perfusion-weighted MR imaging, to our knowledge. Therefore, the aim of this study was to characterize these SIs by using DWI and PWI. DWI would discriminate between vasogenic edema and gliosis, and PWI would demonstrate signs of outflow obstruction and venous congestion.     

Efficacy of Skull Plain Films in Follow-up Evaluation of Cerebral Aneurysms Treated with Detachable Coils: Quantitative Assessment of Coil Mass

BACKGROUND AND PURPOSE:Skull plain films of coiled aneurysms have been used in a limited role, including morphologic comparison of the coil mass. We aimed to evaluate the efficacy of skull plain films in patients treated with detachable coils by using quantitative assessment.MATERIALS AND METHODS:In this retrospective study, 78 pairs of the initial and follow-up skull anteroposterior and lateral images were reviewed independently by 2 neuroradiologists. The largest diameter, the perpendicular diameter, and area of the coil mass were measured separately on plain film, and quantitative changes of parameters were compared between subgroups, which were determined by consensus, depending on the need for retreatment. Subgroup analysis was also performed according to aneurysm size, packing attenuation, and ruptured status.RESULTS:On skull lateral images, mean quantitative changes of the largest diameter (0.53 ± 0.43 mm versus 1.17 ± 0.91 mm, P < .01), the perpendicular diameter (0.56 ± 0.48 mm versus 1.20 ± 1.05 mm, P < .01), and the area of the coil mass (5.21 ± 7.51 mm² versus 10.55 ± 10.93 mm², P < .02) differed significantly between subgroups. Receiver operating characteristic analysis showed quantitative change of the largest diameter (>1.1 mm; sensitivity, 50.0%; specificity, 90.3%), the perpendicular diameter (>.9 mm; sensitivity, 62.5%; specificity, 85.5%), and the area (>8.5 mm²; sensitivity, 50.0%; specificity, 83.9%) on skull lateral films to be indicative of aneurysm recurrence, and the diagnostic accuracy of these parameters increased significantly in the high-packing-attenuation group.CONCLUSIONS:Quantitative measurement of the coil mass by using skull plain lateral images has the potential to predict aneurysm recurrence in follow-up evaluations of intracranial aneurysms with coiling.

Endovascular treatment with detachable coils has proved to be a safe and effective technique for patients with intracranial aneurysm.^1,2 However, the major drawback is that 14%∼33% of coiled aneurysms may be recanalized due to coil compaction, which will need retreatment.^3–5Therefore, follow-up imaging is essential for patients with coiled aneurysms. While DSA is still a criterion standard, MRA is becoming an alternative in follow-up imaging of coiled aneurysms.^6,7 However, these imaging studies have some disadvantages in reality.^8–13In contrast, skull plain films have been conventional imaging tools because they are simple, inexpensive, less invasive, and applicable to every patient under any circumstances. However, the efficacy of skull plain films has been infrequently reported in the follow-up imaging of coiled aneurysms,^14–16 in which the detailed methods used for analysis were obscure and their reliability questionable.We aimed to evaluate the efficacy of skull plain films as follow-up imaging tools of coiled aneurysms by using quantitative assessment and to compare the subgroups by clinical parameters.     

Differentiating Hemangioblastomas from Brain Metastases Using Diffusion-Weighted Imaging and Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted MR Imaging

BACKGROUND AND PURPOSE:On DWI and DSC-PWI, hemangioblastomas and brain metastases may exhibit different signal intensities depending on their cellularity and angiogenesis. The purpose of this study was to evaluate whether a hemangioblastoma can be differentiated from a single brain metastasis with DWI and DSC-PWI.MATERIALS AND METHODS:We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging of 21 patients with hemangioblastomas and 30 patients with a single brain metastasis. Variables of minimum ADC and relative ADC were acquired by DWI and the parameter of relative maximum CBV, by DSC-PWI. Minimum ADC, relative ADC, and relative maximum CBV values were compared between hemangioblastomas and brain metastases by using the nonparametric Mann-Whitney test. The sensitivity, specificity, positive and negative predictive values, accuracy, and the area under the receiver operating characteristic curve were determined.RESULTS:Both the minimum ADC values and relative ADC ratios were significantly higher in hemangioblastomas compared with brain metastases (P < .001 for both minimum ADC values and relative ADC ratios). The same was true for the relative maximum CBV ratio (P < .002). The threshold value of ≥6.59 for relative maximum CBV provided sensitivity, specificity, and accuracy of 95.24%, 53.33%, and 70.59%, respectively, for differentiating hemangioblastomas from brain metastases. Compared with relative maximum CBV, relative ADC had high sensitivity (95.24%), specificity (96.67%), and accuracy (96.08%) using the threshold value of ≥1.54. The optimal threshold value for minimum ADC was ≥1.1 × 10⁻³ mm²/s.CONCLUSIONS:DWI and DSC-PWI are helpful in the characterization and differentiation of hemangioblastomas from brain metastases. DWI appears to be the most efficient MR imaging technique for providing a distinct differentiation of the 2 tumor types.

Hemangioblastomas are benign World Health Organization grade I tumors of vascular origin, which account for 7% of posterior fossa tumors in adults.^1,2 Brain metastases are the most common type of brain malignant neoplasms, and posterior fossa metastases represent about 8.7%–10.9% of all brain metastases.^3–5 Preoperative differentiation of hemangioblastomas and brain metastases is of high clinical relevance because surgical planning, therapeutic decisions, and prognosis vary substantially for each tumor type. In patients with hemangioblastomas, complete surgical resection is the treatment of choice,⁶ whereas patients with brain metastases usually undergo surgery, stereotactic surgery, whole-brain radiation therapy, chemotherapy, or combined therapy.⁷ Furthermore, hemangioblastomas are potentially curable and are often associated with a longer survival.⁸ However, brain metastases are associated with notable mortality and morbidity.⁵ In addition, the surgical resection of hemangioblastomas can be complicated by profuse intraoperative bleeding. Sometimes preoperative embolization of the feeding arteries may reduce the tumor blood supply, which can lessen intraoperative hemorrhage.⁹ In many cases, the 2 entities can be differentiated by using clinical history and conventional MR imaging. However, in some instances, particularly when the clinical findings are noncontributory and hemangioblastomas appear as solid contrast-enhancing masses with peritumoral edema, conventional MR imaging cannot be used to distinguish the 2 tumor types.Because the clinical management and prognosis of these 2 types of tumor are vastly different, it is important to distinguish them with certainty. Advanced MR imaging approaches including DWI and DSC-PWI might complement physiologic information in addition to that obtained with conventional MR imaging. DWI could assess the Brownian movement of water in the microscopic tissue environment and reflect cellularity of the tissue by ADC values, which may aid conventional MR imaging in the characterization of brain tumors and other intracranial diseases.^10–12 DSC-PWI that provides noninvasive morphologic and functional information of the tumor microvasculature can be useful in the preoperative diagnosis and grading of brain tumors. MR imaging parameters of relative cerebral blood volume (rCBV) have become some of the most robust hemodynamic variables used in the characterization of the brain tumors.^13–15 Hemangioblastomas may present with histopathologic structures vastly different from those found in brain metastases. Thus, the application of DWI and DSC-PWI may better evaluate and discriminate the cytostructural and hemodynamic differences between hemangioblastomas and brain metastases.Only a few small studies have evaluated the advanced MR imaging features of a hemangioblastoma,^12,16,17 particularly when assessing their differentiation from a single brain metastasis.¹⁸ The purpose of this study was to evaluate whether a hemangioblastoma can be differentiated from a single brain metastasis with DWI and DSC-PWI.     

Comparison of Perfusion,Diffusion, and MR Spectroscopy between Low-Grade Enhancing Pilocytic Astrocytomas and High-Grade Astrocytomas

BACKGROUND AND PURPOSE:The differentiation of pilocytic astrocytomas and high-grade astrocytomas is sometimes difficult. There are limited comparisons in the literature of the advanced MR imaging findings of pilocytic astrocytomas versus high-grade astrocytomas. The purpose of this study was to assess the MR imaging, PWI, DWI, and MR spectroscopy characteristics of pilocytic astrocytomas compared with high-grade astrocytomas.MATERIALS AND METHODS:Sixteen patients with pilocytic astrocytomas and 22 patients with high-grade astrocytomas (8–66 years of age; mean, 36 ± 17 years) were evaluated by using a 1.5T MR imaging unit. MR imaging, PWI, DWI, and MR spectroscopy were used to determine the differences between pilocytic astrocytomas and high-grade astrocytomas. The sensitivity, specificity, and the area under the receiver operating characteristic curve of all analyzed parameters at respective cutoff values were determined.RESULTS:The relative cerebral blood volume values were significantly lower in pilocytic astrocytomas compared with the high-grade astrocytomas (1.4 ± 0.9 versus 3.3 ± 1.4; P = .0008). The ADC values were significantly higher in pilocytic astrocytomas compared with high-grade astrocytomas (1.5 × 10⁻³ ± 0.4 versus 1.2 × 10⁻³ ± 0.3; P = .01). The lipid-lactate in tumor/creatine in tumor ratios were significantly lower in pilocytic astrocytomas compared with high-grade astrocytomas (8.3 ± 11.2 versus 43.3 ± 59.2; P = .03). The threshold values ≥1.33 for relative cerebral blood volume provide sensitivity, specificity, positive predictive values, and negative predictive values of 100%, 67%, 87%, and 100%, respectively, for differentiating high-grade astrocytomas from pilocytic astrocytomas. The optimal threshold values were ≤1.60 for ADC, ≥7.06 for lipid-lactate in tumor/creatine in tumor, and ≥2.11 for lipid-lactate in tumor/lipid-lactate in normal contralateral tissue.CONCLUSIONS:Lower relative cerebral blood volume and higher ADC values favor a diagnosis of pilocytic astrocytoma, while higher lipid-lactate in tumor/creatine in tumor ratios plus necrosis favor a diagnosis of high-grade astrocytomas.

Pilocytic astrocytoma (PA) is the most common pediatric central nervous system glioma and one of the most common pediatric cerebellar tumors. This tumor occurs most frequently in the first 2 decades of life,¹ composing up to 25% of brain tumors in pediatric neurosurgical practices,² and it only rarely occurs in adults.² The incidence is approximately 4.8 cases per million people per year,³ with 2.3%–6% of all brain tumors classified as PAs.^3,4 PAs are usually clinically benign and are classified as grade I by the World Health Organization (WHO).⁴ They are potentially curable by surgery and are associated with a longer survival.^1,5 Very rarely, a PA may undergo spontaneous malignant transformation and become an anaplastic astrocytoma.⁶A PA typically appears on MR imaging as a large cystic mass with a mural nodule^1,5; however, this pattern can also occur in a hemangioblastoma of the posterior fossa.⁷ MR imaging features of PAs can also be seen in high-grade gliomas (HGGs) and metastases,⁷ particularly when a PA appears as a solidly enhancing mass. Moreover, despite their benign biologic behavior, PAs may be confused with malignant tumors and resemble high-grade astrocytomas (HGAs) on both histopathology and during a neuroimaging evaluation, making the diagnosis difficult.^1,4 This confusion can occur because PAs present a variety of histologic patterns and may have markedly hyalinized and glomeruloid vessels, accompanied by extensive nuclear pleomorphism, which can sometimes make classification a challenge.^1,4Given that differentiation of PAs and HGAs is sometimes challenging to both the neuroradiologist and the pathologist, advanced MR imaging techniques that add functional information to the anatomic MR imaging can be helpful in the characterization and grading of astrocytomas.⁸ Although both PA and HGA belong to the same family of gliomas, a great amount of evidence suggests that PAs present histologic aspects (cellularity, vascularity, cystic formation, necrosis) very distinct from those found in HGAs. Thus, the use of these advanced MR imaging techniques may better evaluate and distinguish the anatomic and functional differences occurring between PAs and HGAs. These include the following: diffusion-weighted imaging (DWI), which evaluates the microstructure and cellularity of brain tissue by analyzing the motion of the water in the tissue⁹; perfusion-weighted imaging (PWI), which evaluates the microvasculature by using relative cerebral blood volume (rCBV)^9,10; and MR spectroscopy, which provides metabolic and histologic marker information about the brain or neoplastic tissue.^9–11There are only a few small series assessing the advanced MR imaging features of PAs, particularly when evaluating neovascularity on PWI^7,12 and their differentiation from HGAs.¹²Our hypothesis is that in comparison with HGAs, PAs present lower cellularity, less vascularity, and a lower metabolism, and each one of these characteristics may be detected with the use of DWI, PWI, and MR spectroscopy, respectively. Therefore, advanced MR imaging techniques should demonstrate findings that may help in the differentiation of PAs from HGAs. The purpose of this study was to assess MR imaging, DWI, PWI, and MR spectroscopy characteristics of PAs compared with HGAs.