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.     

Orbital Lymphoproliferative Disorders (OLPDs): Value of MR Imaging for Differentiating Orbital Lymphoma from Benign OPLDs

BACKGROUND AND PURPOSE:Accurate discrimination of orbital lymphoma from benign orbital lymphoproliferative disorders is crucial for treatment planning. We evaluated MR imaging including DWI and contrast-enhanced MR imaging for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders.MATERIALS AND METHODS:Forty-seven histopathologically proved orbital lymphoproliferative disorders (29 orbital lymphomas and 18 benign orbital lymphoproliferative disorders) were evaluated. Two board-certified radiologists reviewed visual features on T1-weighted, fat-suppressed T2-weighted, diffusion-weighted, and contrast-enhanced MR images. For quantitative evaluation, ADC and contrast-enhancement ratio of all lesions were measured and optimal cutoff thresholds and areas under curves for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders were determined using receiver operative characteristic analysis; corresponding sensitivities and specificities were calculated.RESULTS:Multivariate logistic regression analysis showed that ill-defined tumor margin (P = .003) had a significant association with orbital lymphoma whereas the “flow void sign” (P = .005) and radiologic evidence of sinusitis (P = .0002) were associated with benign orbital lymphoproliferative disorders. The mean ADC and contrast-enhancement ratio of orbital lymphomas were significantly lower than those of benign orbital lymphoproliferative disorders (P < .01). An ADC of less than 0.612 × 10⁻³ mm²/s and a contrast-enhancement ratio of less than 1.88 yielded areas under curves of 0.980 and 0.770, sensitivity of 94.1% and 95.5%, and specificities of 93.3% and 80.0% for predicting orbital lymphoma, respectively.CONCLUSIONS:Some characteristic MR imaging features and quantitative DWI and contrast-enhanced MR imaging are useful in further improving the accuracy of MR imaging for differentiation of orbital lymphoma from benign orbital lymphoproliferative disorders.

Orbital lymphoproliferative disorders (OLPDs) frequently present as an orbital mass lesion (24%–49%) in the adult and comprise a wide spectrum of diseases ranging from benign to malignant lesions.¹ Orbital lymphoma is the most common orbital neoplasm representing 55% of cases in adults.² Most orbital lymphomas are primary, low-grade, B-cell, non-Hodgkin lymphomas, and the most common subtype is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT).³ Other OLPDs comprise several benign, noninfectious, chronic inflammatory diseases, including IgG4-related ophthalmic disease, reactive lymphoid hyperplasia, and idiopathic orbital inflammation.⁴ Among them, IgG4-related ophthalmic disease is becoming increasingly recognized and accounts for approximately half of benign OPLDs on the basis of recent surveillance.⁵ The discrimination of orbital lymphoma from benign OLPDs is crucial because of the different therapeutic implications: the former is amenable to low-dose radiation therapy, whereas the latter are expected to show a good response to corticosteroid therapy.⁶ The utility of conventional anatomic MR imaging for this purpose is limited, however, because orbital lymphoma and benign OLPDs frequently share similar imaging features.^7,8 Recently, some researchers have reported quantitative DWI with ADC measurements to be potentially useful for discriminating orbital lymphoma from other orbital tumors.^9–15 However, these studies included other neoplastic and nonneoplastic lesions such as cavernous hemangiomas, neurogenic tumors, and metastases, and the value of DWI for discrimination of lymphoma and OLPDs remains unclear. The purpose of this study was to assess the value of MR imaging including DWI and contrast-enhanced MR imaging for the discrimination of primary orbital lymphoma from benign OLPDs.     

Imaging Findings in MR Imaging–Guided Focused Ultrasound Treatment for Patients with Essential Tremor

BACKGROUND AND PURPOSE:MR imaging–guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue. The goal of this study was to describe MR imaging findings pre- and post-ventralis intermedius nucleus lesioning by MR imaging–guided focused sonography as a treatment for essential tremor and to determine whether there was an association between these imaging features and the clinical response to MR imaging–guided focused sonography.MATERIALS AND METHODS:Fifteen patients with medication-refractory essential tremor prospectively gave consent; were enrolled in a single-site, FDA-approved pilot clinical trial; and were treated with transcranial MR imaging–guided focused sonography. MR imaging studies were obtained on a 3T scanner before the procedure and 24 hours, 1 week, 1 month, and 3 months following the procedure.RESULTS:On T2-weighted imaging, 3 time-dependent concentric zones were seen at the site of the focal spot. The inner 2 zones showed reduced ADC values at 24 hours in all patients except one. Diffusion had pseudonormalized by 1 month in all patients, when the cavity collapsed. Very mild postcontrast enhancement was seen at 24 hours and again at 1 month after MR imaging–guided focused sonography. The total lesion size and clinical response evolved inversely compared with each other (coefficient of correlation = 0.29, P value = .02).CONCLUSIONS:MR imaging–guided focused sonography can accurately ablate a precisely delineated target, with typical imaging findings seen in the days, weeks, and months following the treatment. Tremor control was optimal early when the lesion size and perilesional edema were maximal and was less later when the perilesional edema had resolved.

MR imaging–guided focused sonography surgery is a new stereotactic technique that uses high-intensity focused sonography to heat and ablate tissue rapidly under closed-loop image guidance and control throughout all steps of the intervention process. MR imaging allows precise intraprocedural localization of the ablation target, verification of safety margins for the sonography treatment, and real-time monitoring of thermal ablation dynamics.^1–7 MR imaging–guided focused sonography is now accepted in the treatment of soft-tissue disorders, including prostate cancer and uterine fibroids. Intracranial applications for brain tumors^8,9 and neuropathic pain syndromes^10,11 are currently under investigation. More recently, MR imaging–guided focused sonography was tested in a clinical trial as a treatment for essential tremor.Essential tremor is a common and disabling movement disorder with an estimated prevalence of 0.3%–5.55%.^12–17 Patients with essential tremor may suffer more from the mental effects on quality of life, such as lower perceived health status,¹⁸ than from actual physical symptoms.¹⁹ Essential tremor may be medically refractory: up to 30% of patients do not respond to first-line therapy and may consider surgical options.²⁰ Improved imaging and refined electrophysiologic localization have demonstrated that the ventralis intermedius nucleus (Vim) of the thalamus is the most effective target. The ventralis intermedius nucleus was the target for the MR imaging–guided focused sonography treatment in the clinical trial mentioned above.The goal of this study was to describe findings on MR imaging both pre- and post-Vim lesioning by MR imaging–guided focused sonography as a treatment for essential tremor in the 15 patients enrolled in the trial and to determine whether there was an association between these imaging features, the number and/or energy of sonications, and the clinical response to MR imaging–guided focused sonography.     

Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation

BACKGROUND AND PURPOSE:Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy.MATERIALS AND METHODS:This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging.RESULTS:MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3–11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions.CONCLUSIONS:The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy.

Uremic encephalopathy is a metabolic disorder that occurs in patients with acute or chronic renal failure. This toxic-metabolic encephalopathy is a complication resulting from endogenous uremic toxins in patients with severe renal failure. The pathogenesis is complex and unclear.Knowledge concerning a uremic encephalopathy (UE)-specific imaging feature, the so-called lentiform fork sign (LFS), is limited to case reports. The LFS may also be present in metabolic acidosis from any cause, including end-stage renal disease, methanol intoxication, and the dialysis disequilibrium syndrome.^1–6 This study was undertaken to describe the MR imaging features in the brains of 10 patients with UE, with the aim of identifying common imaging features and potentially clarifying the possible pathophysiology of UE.     

Differentiation between Treatment-Induced Necrosis and Recurrent Tumors in Patients with Metastatic Brain Tumors: Comparison among 11C-Methionine-PET,FDG-PET,MR Permeability Imaging,and MRI-ADC—Preliminary Results

BACKGROUND AND PURPOSE:In patients with metastatic brain tumors after gamma knife radiosurgery, the superiority of PET using ¹¹C-methionine for differentiating radiation necrosis and recurrent tumors has been accepted. To evaluate the feasibility of MR permeability imaging, it was compared with PET using ¹¹C-methionine, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumors.MATERIALS AND METHODS:The study analyzed 18 lesions from 15 patients with metastatic brain tumors who underwent gamma knife radiosurgery. Ten lesions were identified as recurrent tumors by an operation. In MR permeability imaging, the transfer constant between intra- and extravascular extracellular spaces (/minute), extravascular extracellular space, the transfer constant from the extravascular extracellular space to plasma (/minute), the initial area under the signal intensity–time curve, contrast-enhancement ratio, bolus arrival time (seconds), maximum slope of increase (millimole/second), and fractional plasma volume were calculated. ADC was also acquired. On both PET using ¹¹C-methionine and FDG-PET, the ratio of the maximum standard uptake value of the lesion divided by the maximum standard uptake value of the symmetric site in the contralateral cerebral hemisphere was measured (¹¹C-methionine ratio and FDG ratio, respectively). The receiver operating characteristic curve was used for analysis.RESULTS:The area under the receiver operating characteristic curve for differentiating radiation necrosis from recurrent tumors was the best for the ¹¹C-methionine ratio (0.90) followed by the contrast-enhancement ratio (0.81), maximum slope of increase (millimole/second) (0.80), the initial area under the signal intensity–time curve (0.78), fractional plasma volume (0.76), bolus arrival time (seconds) (0.76), the transfer constant between intra- and extravascular extracellular spaces (/minute) (0.74), extravascular extracellular space (0.68), minimum ADC (0.60), the transfer constant from the extravascular extracellular space to plasma (/minute) (0.55), and the FDG-ratio (0.53). A significant difference in the ¹¹C-methionine ratio (P < .01), contrast-enhancement ratio (P < .01), maximum slope of increase (millimole/second) (P < .05), and the initial area under the signal intensity–time curve (P < .05) was evident between radiation necrosis and recurrent tumor.CONCLUSIONS:The present study suggests that PET using ¹¹C-methionine may be superior to MR permeability imaging, ADC, and FDG-PET for differentiating radiation necrosis from recurrent tumors after gamma knife radiosurgery for metastatic brain tumors.

Stereotactic radiosurgery such as gamma knife radiosurgery (GK) and CyberKnife (Accuray, Sunnyvale, California) is an effective method for treating intracranial neoplasms.^1,2 For metastatic tumors of the brain, stereotactic radiosurgery has generally been the main tool used in therapeutic regimens.^3,4 Although stereotactic radiosurgery is an effective treatment method, it has a risk of radiation necrosis. Radiation necrosis after stereotactic radiosurgery for metastatic tumors of the brain is more common than previously reported.^5,6 It generally occurs 3–12 months after therapy⁷ and often resembles recurrent tumors on conventional imaging techniques, such as MR imaging,^8–11 CT,¹² and SPECT.¹³ Differentiating radiation necrosis and recurrent tumor is extremely important because of the different treatment implications. Histologic examination from a biopsy or resection may aid in differentiating these 2 events. However, a noninvasive method is needed for diagnosing whether a contrast-enhanced lesion with surrounding edema on conventional MR imaging is radiation necrosis or a recurrent tumor.Advanced MR imaging techniques including MR spectroscopy,¹⁴ DWI,¹⁵ and DTI¹⁶ have been used for differentiation of radiation necrosis and recurrent tumors. The CTP technique has also been reported as promising in this field.¹⁷ CTP has the advantage of using widely available CT scanners, though x-ray exposure and administration of ionizing contrast material limit the clinical use. In radionuclide studies, SPECT with ²⁰¹TI-chloride,¹⁸ technetium Tc99m-sestamibi,^{19 123}I-alfa-methyl-L-tyrosine,²⁰O-(2-[¹⁸F]-fluoroethyl)-L-tyrosine (FET-PET),^21,22 6-[¹⁸F]-fluoro-L-dopa (FDOPA),²³ and FDG-PET^24–26 have been reported to differentiate between radiation necrosis and recurrent tumors. Compared with those studies, the superiority of PET with ¹¹C-methionine (MET) for differentiating radiation necrosis and recurrent tumors has been accepted because of the high sensitivity and specificity.^27–31 However, MET-PET is not widely available. Dynamic contrast-enhanced MR imaging with a contrast agent has been used to characterize brain tumors^32,33 and stroke.³⁴MR permeability imaging with dynamic contrast-enhanced–MR imaging based on the Tofts model³⁵ has recently been developed and used for evaluating cerebrovascular diseases,³⁶ brain tumors,^37–39 nasopharyngeal carcinomas,^40,41 rectal carcinomas,⁴² and prostate carcinomas.⁴³ The endothelial permeability of vessels in brain tumors can be quantitatively acquired with MR permeability imaging. The vascular microenvironment in tumors can be measured by parameters such as influx transfer constant, reverse transfer constant, and the extravascular extracellular space.⁴⁴ These parameters may reflect tissue characteristics including vascular density, a damaged blood-brain barrier, vascularity, and neoangiogenesis.⁴⁴ If the feasibility of MR permeability imaging for differentiating radiation necrosis and recurrent tumors could be demonstrated, this technique may contribute to the management of patients after stereotactic radiosurgery and conventional radiation therapy because MR permeability imaging is widely available. To evaluate the feasibility of MR permeability imaging in the present study, we compared it with MET-PET, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumor after GK in patients with metastatic brain tumors.     

MR Imaging Grading System for Skull Base Chordoma

BACKGROUND AND PURPOSE:Skull base chordoma has been widely studied in recent years, however, imaging characteristics of this tumor have not been well elaborated. The purpose of this study was to establish an MR imaging grading system for skull base chordoma.MATERIALS AND METHODS:In this study, 156 patients with skull base chordomas were retrospectively assessed. Tumor-to-pons signal intensity ratios were calculated from pretreatment MR images R_T1 (ratio of tumor to pons signal intensity in T1 FLAIR sequence), R_T2 (ratio of tumor to pons signal intensity in T2 sequence) and R_EN (ratio of tumor to pons signal intensity in enhanced T1 FLAIR sequence), and significant ratios for overall survival and progression-free survival were selected to establish a grading system. Clinical variables among different MR imaging grades were then analyzed to evaluate the usefulness of the grading system.RESULTS:R_T2 (P < .001) and R_EN (P = .04) were identified as significant variables affecting progression-free survival. After analysis, the classification criteria were set as follows: MR grade I, R_T2 > 2.49 and R_EN ≤ 0.77; MR grade II, R_T2 > 2.49 and R_EN > 0.77, or R_T2 ≤ 2.49 and R_EN ≤ 0.77; and MR grade III, R_T2 ≤ 2.49 and R_EN > 0.77. MR grade III tumors had a more abundant tumor blood supply than MR grade I tumors (P < .001), and the intraoperative blood loss of MR grade III tumors was higher than that of MR grade I tumors (P = .002). Additionally, skull base chordoma progression risk increased by 2.071 times for every single MR grade increase (P < .001).CONCLUSIONS:A higher R_T2 value was a negative indicator of tumor progression, whereas a higher R_EN value was a positive risk factor of tumor progression. MR grade III tumors showed a more abundant blood supply than MR grade I tumors, and the risk of skull base chordoma progression increased with every single MR grade increase.

Chordoma is a malignant tumor that originates from notochord remnants, and this tumor often exhibits mild-to-moderate enhancement. It comprises 1.8%–4.3% of bone tumors and 3.9%–6.1% of malignant bone tumors,^1–3 and it shows a marked predilection for the axial skeleton. Chordoma primarily occurs in the skull base (32%–42%) and sacrococcygeal region (29.2%).^4,5 The prevalence of chordomas is 0.08–0.089 per 100,000, and males (0.01–0.016 per 100,000) have a higher incidence than females (0.06–0.066 per 100,000).^4–6 Chordoma is locally aggressive and may destroy surrounding bone. Skull base chordoma (SBC) often involves vital blood vessels, cranial nerves, and other important structures. Extensive resection of a skull base chordoma is difficult and may result in severe complications.⁷ Chemotherapy usually has a minimal effect on chordomas, and the current best treatment is radical resection plus postoperative radiation therapy.^8,9 The median survival for patients with SBC is 151 months.¹⁰ In recent years, new technologies such as endoscopy, intraoperative navigation, and electrophysiologic monitoring have facilitated more radical resections.¹¹ Although the proton beam, carbon ion, modulated and stereotactic techniques were applied in radiation therapy, the progression and mortality rates of skull base chordoma are still very high.^11–14The diagnosis and classification of chordoma primarily depend on histopathologic evaluation and preoperative imaging data. Chordoma has 3 histologic types: conventional, chondroid, and dedifferentiated.¹⁵ Conventional chordoma is the most common type, and patients with chondroid chordoma are reported to have the best prognoses.⁸ Chordoma often shows low density and bone destruction on CT.¹⁶ MR imaging is superior in detecting the tumor and delineating its extent.¹⁷ Chordomas have a highly heterogeneous appearance on MR imaging, demonstrating hypo- to isointensity on T1 sequences and moderate-to-very-high intensity on T2 sequences. The tumor may exhibit minimal-to-moderate enhancement on enhanced T1 sequences (Fig 1). The clinical significance of this MR imaging heterogeneity has not been discussed in the literature, to our knowledge.Open in a separate windowFig 1.MR imaging of 2 patients with SBC. Patient 1 (A–C), 21-years of age. Pathologic findings were conventional chordoma. The patient underwent subtotal tumor resection with no progression at 48 months. A, Axial T2-weighted MR imaging. Tumor demonstrates homogeneous high signal intensity. B, Axial T1 FLAIR-weighted MR imaging. Tumor has relatively homogeneous hypointense signal compared with the pons. C, Enhanced T1 FLAIR MR imaging shows no enhancement of the lesion. Patient 2 (D–F), 25 years of age. Pathologic findings revealed conventional chordoma with necrosis and nuclear division. This patient underwent subtotal tumor resection with tumor progression at 8 months. D, Axial T2-weighted MR imaging demonstrates tumor heterogeneity. The signal intensity is relatively lower than that in patient 1. E, Axial T1 FLAIR MR imaging. The tumor is heterogeneous and hyperintense compared with the pons. F, Enhanced T1 FLAIR MR imaging. Tumor exhibits moderate enhancement.We thought that the clinical features and prognosis of SBCs were associated with the characteristics on MR imaging (Figs 1 and ​and2).2). The purpose of this study was to explore the value of MR signal intensity (SI) in establishing a grading system for SBC.Open in a separate windowFig 2.Kaplan-Meier analysis illustrating survival (left) and progression-free survival (right) for different MR imaging grades. There were no differences in overall survival among the 3 MR grade groups (log-rank = 1.669, P = .43). Progression-free survival was different among the 3 MR grades (log-rank = 25.889, P < .001), with grade III tumors being associated with shorter progression-free survival than grade I (log-rank = 18.561, P < .001) and grade II (log-rank = 12.668, P < .001) tumors.     

Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype

BACKGROUND AND PURPOSE:The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.MATERIALS AND METHODS:Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study.RESULTS:There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm³ versus 35.1–47.6 cm³; P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04).CONCLUSIONS:MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

Medulloblastomas (World Health Organization [WHO] grade IV) rarely occur in adults. According to the United States registry analysis from the Surveillance, Epidemiology, and End-Results data base, incidence rates around 0.6 cases per million have been recorded, which is >50 times lower than the incidence of glioblastoma.^1–3 A higher age at diagnosis is a negative prognostic factor for survival, with a median overall survival currently between 7.7 and 9.7 years, provided patients receive the best medical care.⁴ The 2016 revision of the WHO classification of CNS tumors introduced the concept of an integrative medulloblastoma diagnosis.⁵ The diagnosis includes 4 histologically and 4 genetically defined entities known to have an influence on the course of the disease in both children and adults.^6–12 The genetic entities that are currently defined are sonic hedgehog (SHH)-activated (and exist with or without TP53 mutation), wingless (WNT)-activated, and non-SHH/non-WNT (Groups 3 and 4) medulloblastomas. The defined histologic groups are classic (CMB), large cell anaplastic, desmoplastic/nodular (DNMB) medulloblastomas and medulloblastoma of extensive nodularity. The exact classification at the earliest possible time point is of great importance to evaluate prognosis and possible targeted therapies.Radiogenomics is a dynamically evolving field in radiology based on standard diagnostic MR imaging. It seeks to identify so-called MR imaging biomarkers that may predict the genetic profile of a tumor, assuming that the genetic profile is reflected in a distinctive radiophenotype, and can also be of benefit when true genetic analysis is not available.¹³ Only 1 study has been published in a predominantly pediatric cohort, which investigated a radiogenomic approach to differentiate genetically defined medulloblastoma entities.¹⁴ The authors found that genetic entities were distinguishable by several MR imaging biomarkers such as tumor location or enhancement pattern. Different relative frequencies and varying prognostic influences of the genetic medulloblastoma entities between adult and pediatric cohorts suggest that MR imaging biomarkers identified in pediatric cohorts may be different from those in adult medulloblastoma.^{8–10,12,15,16}The Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-07) is the first prospective trial of an adult medulloblastoma cohort that systematically evaluated radiochemotherapy as the first-line treatment and included, among others, imaging biomarkers in its analysis. The study presented here is dedicated to identifying MR imaging biomarkers that will allow differentiation of medulloblastoma genetic entities based on the entirely adult NOA-07 cohort. Identification of such MR imaging biomarkers may facilitate presurgical tumor assessment and assist in the categorization of the differences between adult and pediatric MR imaging biomarkers.     

Comparison of High-Resolution MR Imaging and Digital Subtraction Angiography for the Characterization and Diagnosis of Intracranial Artery Disease

BACKGROUND AND PURPOSE:High-resolution MR imaging has recently been introduced as a promising diagnostic modality in intracranial artery disease. Our aim was to compare high-resolution MR imaging with digital subtraction angiography for the characterization and diagnosis of various intracranial artery diseases.MATERIALS AND METHODS:Thirty-seven patients who had undergone both high-resolution MR imaging and DSA for intracranial artery disease were enrolled in our study (August 2011 to April 2014). The time interval between the high-resolution MR imaging and DSA was within 1 month. The degree of stenosis and the minimal luminal diameter were independently measured by 2 observers in both DSA and high-resolution MR imaging, and the results were compared. Two observers independently diagnosed intracranial artery diseases on DSA and high-resolution MR imaging. The time interval between the diagnoses on DSA and high-resolution MR imaging was 2 weeks. Interobserver diagnostic agreement for each technique and intermodality diagnostic agreement for each observer were acquired.RESULTS:High-resolution MR imaging showed moderate-to-excellent agreement (interclass correlation coefficient = 0.892–0.949; κ = 0.548–0.614) and significant correlations (R = 0.766–892) with DSA on the degree of stenosis and minimal luminal diameter. The interobserver diagnostic agreement was good for DSA (κ = 0.643) and excellent for high-resolution MR imaging (κ = 0.818). The intermodality diagnostic agreement was good (κ = 0.704) for observer 1 and moderate (κ = 0.579) for observer 2, respectively.CONCLUSIONS:High-resolution MR imaging may be an imaging method comparable with DSA for the characterization and diagnosis of various intracranial artery diseases.

Intracranial artery disease (ICAD) is one of the major causes of ischemic stroke and neurologic symptoms.^1–3 ICAD generally presents with intracranial artery stenosis on luminal evaluation, even though it includes various ICADs, such as atherosclerosis, dissection, Moyamoya disease, and vasculitis. The degree of stenosis has been the most common and important characteristic for evaluating ICAD and determining the treatment options.^4,5Luminal angiography, such as digital subtraction angiography, CT angiography, and MR angiography, has been widely used and has functioned successfully for the evaluation of stenosis and the diagnosis of ICAD. Among these methods, DSA is thought to be the criterion standard tool compared with the other modalities because it depicts luminal geometric shapes and hemodynamic information with higher resolution.^6–8 However, DSA has several limitations. It only depicts the luminal morphology and not the vessel walls directly, and many diseases share nonspecific luminal findings. Because DSA is also an invasive procedure with the risk of neurologic complications and radiation exposure, it is not suitable for screening or serial examinations.^9–11 Accordingly, CTA and MRA have been commonly used as the minimally invasive method to diagnose and differentiate intracranial artery disease in the clinical field, though they have more drawbacks in the luminal evaluation to DSA.High-resolution MR imaging (HR-MR) has recently been introduced as a minimally invasive and promising advanced imaging technique for directly depicting the intracranial arterial wall.^12,13Although HR-MR evaluates and differentiates various ICADs with the direct depiction of arterial walls and multicontrast images^6,14–20 that may correlate with luminal angiography,^8,21,22 the usefulness and value of HR-MR compared with luminal angiography are still unclear. Only a few studies presented a comparison or correlation between DSA and HR-MR,^8,13,23 and these studies showed a good correlation regarding the degree of stenosis^8,23 and HR-MR features beyond DSA.¹³ However, the observations were based on single vascular pathology or a single cerebral artery (middle cerebral artery, basilar artery) or a small sample size (n = 9).In our study, we compared HR-MR with DSA in the characterization and diagnosis of various ICADs. We hypothesized that HR-MR may be an imaging method comparable with DSA for the characterization and diagnosis of ICAD.     

Early-Stage Glioblastomas: MR Imaging–Based Classification and Imaging Evidence of Progressive Growth

BACKGROUND AND PURPOSE:The serial imaging changes describing the growth of glioblastomas from small to large tumors are seldom reported. Our aim was to classify the imaging patterns of early-stage glioblastomas and to define the order of appearance of different imaging patterns that occur during the growth of small glioblastomas.MATERIALS AND METHODS:Medical records and preoperative MR imaging studies of patients diagnosed with glioblastoma between 2006 and 2013 were reviewed. Patients were included if their MR imaging studies showed early-stage glioblastomas, defined as small MR imaging lesions detected early in the course of the disease, demonstrating abnormal signal intensity but the absence of classic imaging findings of glioblastoma. Each lesion was reviewed by 2 neuroradiologists independently for location, signal intensity, involvement of GM and/or WM, and contrast-enhancement pattern on MR imaging.RESULTS:Twenty-six patients with 31 preoperative MR imaging studies met the inclusion criteria. Early-stage glioblastomas were classified into 3 types and were all hyperintense on FLAIR/T2-weighted images. Type I lesions predominantly involved cortical GM (n = 3). Type II (n = 12) and III (n = 16) lesions involved both cortical GM and subcortical WM. Focal contrast enhancement was present only in type III lesions at the gray-white junction. Interobserver agreement was excellent (κ = 0.95; P < .001) for lesion-type classification. Transformations of lesions from type I to type II and type II to type III were observed on follow-up MR imaging studies. The early-stage glioblastomas of 16 patients were pathologically confirmed after imaging progression to classic glioblastoma.CONCLUSIONS:Cortical lesions may be the earliest MR imaging–detectable abnormality in some human glioblastomas. These cortical tumors may progress to involve WM.

Glioblastoma (GB) is the most common primary malignant brain tumor. It typically appears as a large mass with necrosis, prominent edema, mass effect, and strong heterogeneous contrast enhancement when diagnosed. MR imaging, a noninvasive diagnostic tool with excellent tissue contrast, has the potential to detect small GBs. However, it is uncommon to detect small GBs clinically, probably due to nonspecific or absent symptoms. The serial imaging changes depicting the growth of GBs from small to large tumors are seldom reported.Some reports described small MR imaging lesions that subsequently progressed to GBs.^1–11 These are often described as ill-defined, FLAIR or T2-weighted hyperintensities without discernable mass effect that typically involve both the cortex and subcortical WM, but occasionally appear as only cortical lesions.^2,4,8 Contrast enhancement is not a consistent feature and tends to be focal and nodular when present.^6–8 The commonly affected brain areas include frontal (n = 4),^2,3,6,8 parietal (n = 2),^7,10 occipital (n = 1),¹¹ temporal (n = 5),^2,3,6,7,11 hippocampal (n = 3),^1,2,9 and insular (n = 1)⁹ regions. Because these MR imaging lesions were detected early in the course of the disease, they were frequently referred to as early-stage GBs.^3,5–8,11We have noticed different imaging patterns in early-stage GBs. An imaging classification for early-stage GB, however, is not available because most previous studies included only a few such cases. It is important for radiologists to be familiar with early imaging findings and growth patterns of GBs because familiarity may help diagnose small tumors that are symptomatic or incidentally found. Early diagnosis of GB may lead to a higher extent of tumor resection, which has been demonstrated to correlate with patient survival.¹² In this study, we aimed to classify the imaging patterns of early-stage GBs and to the define the order of appearance of different imaging patterns that occur during the growth of these tumors.     

Chordoid Meningioma: Differentiating a Rare World Health Organization Grade II Tumor from Other Meningioma Histologic Subtypes Using MRI

BACKGROUND AND PURPOSE:Meningiomas are very commonly diagnosed intracranial primary neoplasms, of which the chordoid subtype is seldom encountered. Our aim was to retrospectively review preoperative MR imaging of intracranial chordoid meningiomas, a rare WHO grade II variant, in an effort to determine if there exist distinguishing MR imaging characteristics that can aid in differentiating this atypical variety from other meningioma subtypes.MATERIALS AND METHODS:Ten cases of WHO grade II chordoid meningioma were diagnosed at our institution over an 11-year span, 8 of which had preoperative MR imaging available for review and were included in our analysis. Chordoid meningioma MR imaging characteristics, including ADC values and normalized ADC ratios, were compared with those of 80 consecutive cases of WHO grade I meningioma, 21 consecutive cases of nonchordoid WHO grade II meningioma, and 1 case of WHO grade III meningioma.RESULTS:Preoperative MR imaging revealed no significant differences in size, location, signal characteristics, or contrast enhancement between chordoid meningiomas and other meningiomas. There were, however, clear differences in the ADC values and normalized ADC ratios, with a mean absolute ADC value of 1.62 ± 0.33 × 10⁻³ mm²/s and a mean normalized ADC ratio of 2.22 ± 0.47 × 10⁻³ mm²/s in chordoid meningiomas compared with mean ADC and normalized ADC values, respectively, of 0.88 ± 0.13 × 10⁻³ mm²/s and 1.17 ± 0.16 × 10⁻³ mm²/s in benign WHO grade I meningiomas, 0.84 ± 0.11 × 10⁻³ mm²/s and 1.11 ± 0.15 × 10⁻³ mm²/s in nonchordoid WHO grade II meningiomas, and 0.57 × 10⁻³ mm²/s and 0.75 × 10⁻³ mm²/s in the 1 WHO grade III meningioma.CONCLUSIONS:Chordoid meningiomas have statistically significant elevations of ADC and normalized ADC values when compared with all other WHO grade I, II, and III subtypes, which enables reliable preoperative prediction of this atypical histopathologic diagnosis.

Meningiomas are the second most common primary intracranial neoplasm, constituting approximately 13%–25% of such tumors.¹ There are 15 variants of meningioma according the 2007 World Health Organization (WHO) classification of tumors of the central nervous system.² Although 80%–90% of meningiomas are classified as benign WHO grade I tumors, WHO grade II and III varieties demonstrate a more aggressive clinical course and have a greater propensity for recurrence, and the grade and extent of original resection accounts for these differences.³ Ideally, preoperative imaging to identify the potentially more aggressive grade II and III varieties would be helpful for presurgical planning and subsequent imaging follow-up. One such rare variant is the WHO grade II chordoid meningioma. A little more than 100 cases of chordoid meningioma have been described in the English-language literature, the majority of which are in the pathology and neurosurgery literature.^4–9Attempts to distinguish benign from atypical and malignant meningiomas have been undertaken with variable results, and DWI and ADC values have provided the most reliable means of differentiation,^10,11 though no data analysis specifically examining the chordoid morphologic variant has been performed. To the best of our knowledge, only 3 case reports in which the MR imaging characteristics of chordoid meningiomas were described have been published in the radiology literature.^12–14We compared 8 cases of intracranial chordoid meningioma to 80 consecutive cases of WHO grade I meningioma, 21 consecutive cases of nonchordoid WHO grade II meningioma, and 1 WHO grade III meningioma in an effort to determine if there exist distinguishing MR imaging characteristics that can aid in differentiating this particular subtype.     

Assessment of MR Imaging and CT in Differentiating Hereditary and Nonhereditary Paragangliomas

BACKGROUND AND PURPOSE:Head and neck paragangliomas have been reported to be associated with mutations of the succinate dehydrogenase enzyme family. The aim of this study was to assess whether radiologic features could differentiate between paragangliomas in the head and neck positive and negative for the succinate dehydrogenase mutation.MATERIALS AND METHODS:This single-center retrospective review from January 2015 to January 2020 included 40 patients with 48 paragangliomas (30 tumors positive for succinate dehydrogenase mutation in 23 patients and 18 tumors negative for the succinate dehydrogenase mutation in 17 patients). ADC values and tumor characteristics on CT and MR imaging were evaluated by 2 radiologists. Differences between the 2 cohorts in the diagnostic performance of ADC and normalized ADC (ratio to ADC in the medulla oblongata) values were evaluated using the independent samples t test. P < .05 was considered significant.RESULTS:ADC_mean (1.07 [SD, 0.25]/1.04 [SD, 0.12] versus 1.31 [SD, 0.16]/1.30 [SD, 0.20]× 10⁻³ mm²/s by radiologists 1 and 2; P < .001), ADC_maximum (1.49 [SD, 0.27]/1.49 [SD, 0.20] versus 2.01 [SD, 0.16]/1.87 [SD, 0.20] × 10⁻³ mm²/s; P < .001), normalized ADC_mean (1.40 [SD, 0.33]/1.37 [SD, 0.16] versus 1.73 [SD, 0.22]/1.74 [SD, 0.27]; P < .001), and normalized ADC_maximum (1.95 [SD, 0.37]/1.97 [SD, 0.27] versus 2.64 [SD, 0.22]/2.48 [SD, 0.28]; P < .001) were significantly lower in succinate dehydrogenase mutation–positive than mutation–negative tumors. ADC_minimum, normalized ADC_minimum, and tumor characteristics were not statistically significant.CONCLUSIONS:ADC is a promising imaging biomarker that can help differentiate succinate dehydrogenase mutation–positive from mutation–negative paragangliomas in the head and neck.

Paragangliomas are uncommon neuroendocrine tumors with an estimated annual incidence of 3–8 cases per 1 million people in the general population.¹ They arise from the sympathetic and parasympathetic autonomic system and occur anywhere from the base of the skull to the pelvis, with 70% of extra-adrenal paragangliomas arising in the head and neck region. The typical clinical sites are the carotid artery bifurcation, middle ear, and jugular fossa.^1-3 Clinical manifestations include hypertension, palpitations, headache, excessive sweating, and pallor, which vary depending on the tumor size, location, and biochemical activity.^1,4There has been an increasing interest in the genetic basis for paragangliomas. Although head and neck paragangliomas often occur as sporadic tumors, it is now recognized that approximately 30%–40% of head and neck paragangliomas are associated with autosomal dominant hereditary tumor syndromes.^1,2,5 Succinate dehydrogenase (SDH), a multiprotein complex composed of SDH subunit A, B, C, and D proteins, is an important enzyme in the Krebs cycle and electron transport chain in the mitochondria for energy production. The loss of SDH function results in less efficiency of these processes. Moreover, these altered pathways allow the tumor cells to grow even in a low-oxygen environment.⁶ Therefore, deactivation in any of the subunits will result in tumors positive for the SDH mutation.Familial paraganglioma syndromes associated with SDH gene mutations have now been recognized as the primary cause of hereditary paragangliomas in the head and neck. Twenty-five percent of all paragangliomas and pheochromocytomas are related to genetic mutations in different subunits of the SDH protein, each with different tendencies toward different tumor locations, different numbers of lesions, and different potentials for malignancy.¹ For example, familial paragangliomas with SDH subunit D (SDHD) mutation are more likely to be multifocal in the head and neck, and paragangliomas with SDH subunit B (SDHB) mutations are prone to malignant transformation.¹ Therefore, establishment of genetic screening of individuals and life-long surveillance of patients at high risk for developing paragangliomas are important.The typical imaging appearances of head and neck paragangliomas on CT and MR imaging include well-circumscribed lesions showing avid contrast enhancement.^7-9 Prior studies have demonstrated that DWI and ADC parameters can be used for diagnosis, staging, and follow-up of head and neck tumors.¹⁰ As for paragangliomas, ADC values have been used in the past to differentiate these tumors from other head and neck lesions, with variable results.¹¹ Because paragangliomas can have genetic mutations and a variety of histologic patterns,¹² the variability of ADC values on MR imaging studies may be secondary to the heterogeneous genotype of these lesions. The aim of our study, therefore, was to evaluate the differences in ADC values between SDH mutation–positive and SDH mutation–negative head and neck paragangliomas to assess the utility of ADC as an imaging biomarker.     

Minimizing Radiation Exposure in Evaluation of Pediatric Head Trauma: Use of Rapid MR Imaging

BACKGROUND AND PURPOSE:With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to assess the validity of rapid MR imaging to replace CT in the follow-up imaging of patients with head trauma.MATERIALS AND METHODS:A retrospective review of 103 pediatric patients who underwent initial head CT and subsequent follow-up rapid MR imaging between January 2010 and July 2013 was performed. Patients had minor head injuries (Glasgow Coma Scale, >13) that required imaging. Initial head CT was performed, with follow-up rapid MR imaging completed within 48 hours. A board-certified neuroradiologist, blinded to patient information and scan parameters, then independently interpreted the randomized cases.RESULTS:There was almost perfect agreement in the ability to detect extra-axial hemorrhage on rapid MR imaging and CT (κ = 0.84, P < .001). Evaluation of hemorrhagic contusion/intraparenchymal hemorrhage demonstrated a moderate level of agreement between MR imaging and CT (κ = 0.61, P < .001). The ability of MR imaging to detect a skull fracture also showed a substantial level of agreement with CT (κ = 0.71, P < .001). Detection of diffuse axonal injury demonstrated a slight level of agreement between MR imaging and CT (κ = 0.154, P = .04). However, the overall predictive agreement for the detection of an axonal injury was 91%.CONCLUSIONS:Rapid MR imaging is a valid technique for detecting traumatic cranial injuries and an adequate examination for follow-up imaging in lieu of repeat CT.

Head trauma continues to be a leading cause of death and disability in children in the United States.¹ Every year, >473,000 visits to the emergency department are related to brain injury,² most resulting from minor injuries or falls. Although most head injuries are classified as mild, approximately 10%–15% of children sustain a severe one. The incidence of intracranial injury following minor head trauma is unknown; however, with increasing public awareness of traumatic brain injury and concussion, there has been a rise in research of minor head injuries. Methods of diagnosis,^3,4 hospital admission criteria,^5,6 and return-to-play criteria^7,8 are a few of the active areas of research.Children with head trauma, at risk for intracranial injury, should be initially imaged with CT⁹ because it remains the criterion standard technique for the evaluation of head trauma.¹⁰ Although the incidence of injuries requiring neurosurgical intervention in children with minor head injuries is low, the use of CT for evaluation has been increasing. The use of CT increased from 13% to 22% from 1995 to 2003, with a peak of 29% in 2000.¹¹ The decision to obtain neuroimaging for children with minor head trauma must balance the importance of identifying head injuries with the risks of CT. There is growing awareness in the medical community and public of increased cancer risk caused by ionizing radiation.¹² Brenner et al¹³ estimated that 170 additional fatal cancers will develop due to head CT examinations performed in children younger than 15 years of age in the United States in a single year. In addition, some children may require sedation to obtain an adequate CT examination, which can be associated with as high as a 20.1% chance of an adverse event.¹⁴MR imaging is an alternative technique that avoids ionizing radiation exposure altogether and produces high-quality images. A study with conventional sequences requires long acquisition times and is susceptible to motion artifacts. The need for sedation increases the risk to the patient, lengthens the time needed to acquire patient images, and further increases the cost of standard MR imaging.^14,15Modified MR imaging protocols with reduced acquisition times have been used successfully in non-neurosurgical patients,^16,17 and rapid MR imaging (rMRI) or “quick-brain” MR imaging protocols have become an accepted technique to evaluate and follow patients with hydrocephalus.^18–20 Missios et al²¹ investigated the use of rMRI in patients without hydrocephalus and concluded that it was an adequate neuroimaging tool for evaluation and follow-up. The use of rMRI protocols in evaluating pediatric patients with minor head injuries remains to be validated.As far as we are aware, a systematic search of current literature did not yield a previous study examining the validity of rMRI in the imaging of pediatric patients with head trauma. The purpose of our study was to demonstrate the efficacy of replacing ionizing CT imaging with nonionizing rMRI for follow-up of patients with minor head trauma.     

Detection and Grading of Endolymphatic Hydrops in Menière Disease Using MR Imaging

BACKGROUND AND PURPOSE:Endolymphatic hydrops has been recognized as the underlying pathophysiology of Menière disease. We used 3T MR imaging to detect and grade endolymphatic hydrops in patients with Menière disease and to correlate MR imaging findings with the clinical severity.MATERIALS AND METHODS:MR images of the inner ear acquired by a 3D inversion recovery sequence 4 hours after intravenous contrast administration were retrospectively analyzed by 2 neuroradiologists blinded to the clinical presentation. Endolymphatic hydrops was classified as none, grade I, or grade II. Interobserver agreement was analyzed, and the presence of endolymphatic hydrops was correlated with the clinical diagnosis and the clinical Menière disease score.RESULTS:Of 53 patients, we identified endolymphatic hydrops in 90% on the clinically affected and in 22% on the clinically silent side. Interobserver agreement on detection and grading of endolymphatic hydrops was 0.97 for cochlear and 0.94 for vestibular hydrops. The average MR imaging grade of endolymphatic hydrops was 1.27 ± 0.66 for 55 clinically affected and 0.65 ± 0.58 for 10 clinically normal ears. The correlation between the presence of endolymphatic hydrops and Menière disease was 0.67. Endolymphatic hydrops was detected in 73% of ears with the clinical diagnosis of possible, 100% of probable, and 95% of definite Menière disease.CONCLUSIONS:MR imaging supports endolymphatic hydrops as a pathophysiologic hallmark of Menière disease. High interobserver agreement on the detection and grading of endolymphatic hydrops and the correlation of MR imaging findings with the clinical score recommend MR imaging as a reliable in vivo technique in patients with Menière disease. The significance of MR imaging detection of endolymphatic hydrops in an additional 22% of asymptomatic ears requires further study.

According to the 1985 American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines, Menière disease (MD) is defined by ≥2 definitive spontaneous episodes of vertigo 20 minutes or longer, audiometrically documented hearing loss on at least 1 occasion, and tinnitus or aural fullness.¹ In 1995, a clinical diagnostic scale was added with the categories possible, probable, definite, and certain,² with “certain” defined as definite disease plus histopathologic confirmation. It is universally agreed that the pathogenesis of MD consists of endolymphatic hydrops (EH), but a simple cause-effect relation between EH and clinical symptoms is not present. Moreover, EH appears to be an end point of different etiologies such as trauma,² viral infection and autoimmune processes,³ electrolyte imbalance,⁴ and cellular channelopathies.⁵ Histopathology has provided evidence that not every individual with EH presents with symptoms of MD^6–8 and not every individual with the clinical diagnosis of MD has EH.^9–12 Only recently has MR imaging enabled depiction of EH,¹³ opening a window for in vivo confirmation of EH. The purpose of our study was to assess the degree of EH in 53 patients with MD and to correlate the MR imaging findings obtained by a specific protocol with the certitude of clinical diagnosis.     

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.     

Added Value of Arterial Spin-Labeling MR Imaging for the Differentiation of Cerebellar Hemangioblastoma from Metastasis

BACKGROUND AND PURPOSE:In adults with only cerebellar masses, hemangioblastoma and metastasis are the 2 most important differential diagnoses. Our aim was to investigate the added value of arterial spin-labeling MR imaging for differentiating hemangioblastoma from metastasis in patients with only cerebellar masses.MATERIALS AND METHODS:This retrospective study included a homogeneous cohort comprising patients with only cerebellar masses, including 16 hemangioblastomas and 14 metastases. All patients underwent enhanced MR imaging, including arterial spin-labeling. First, the presence or absence of a hyperperfused mass was determined. Next, in the hyperperfused mass, relative tumor blood flow (mean blood flow in the tumor divided by blood flow measured in normal-appearing cerebellar tissue) and the size ratio (size in the arterial spin-labeling images divided by size in the postcontrast T1WI) were measured. To validate the arterial spin-labeling findings, 2 observers independently evaluated the conventional MR images and the combined set of arterial spin-labeling images.RESULTS:All patients with hemangioblastomas and half of the patients with metastases presented with a hyperperfused mass (P < .001). The size ratio and relative tumor blood flow were significantly larger for hemangioblastomas than for metastases (P < .001 and P = .039, respectively). The size ratio revealed excellent diagnostic power (area under the curve = 0.991), and the relative tumor blood flow demonstrated moderate diagnostic power (area under the curve = 0.777). The diagnostic accuracy of both observers was significantly improved after the addition of arterial spin-labeling; the area under the curve improved from 0.574 to 0.969 (P < .001) for observer 2 and from 0.683 to 1 (P < .001) for observer 2.CONCLUSIONS:Arterial spin-labeling imaging can aid in distinguishing hemangioblastoma from metastasis in patients with only cerebellar masses.

Hemangioblastoma and metastasis are the 2 most important differential diagnoses of cerebellar masses in adults. Hemangioblastomas are benign tumors of vascular origin and are the second most common infratentorial parenchymal tumor, accounting for 7% of posterior fossa tumors in adults.¹ Metastases are the most common type of brain tumor, and posterior fossa metastases represent approximately 8.7%–10.9% of all brain metastases.^2,3 Discriminating between hemangioblastoma and brain metastasis is important because their therapeutic approaches and prognoses are quite different. The standard treatment for hemangioblastoma is complete surgical resection. However, patients with a brain metastasis usually undergo surgery, stereotactic surgery, whole-brain radiation therapy, chemotherapy, or a combination of these. Furthermore, hemangioblastomas are associated with longer patient survival times,⁴ whereas brain metastases are associated with a poor prognosis.⁵ Because the frequency of metastasis increases with time, patient age is often helpful in distinguishing between these tumors but is not always reliable. In addition, although one-third of patients with cerebellar hemangioblastomas also have von Hippel-Lindau disease,⁶ a clinical history of von Hippel-Lindau disease may not be available at the time of initial presentation.Hemangioblastoma is characterized by markedly increased vascularity⁷; therefore, angiographically dense tumor staining may suggest hemangioblastoma rather than metastasis.⁸ However, cerebral angiography is invasive and involves risks of complications, such as stroke. MR perfusion imaging can provide useful information about vascularization in hemangioblastoma. Previous studies using dynamic susceptibility contrast and dynamic contrast-enhanced MR perfusion imaging have reported increased vascular perfusion in hemangioblastomas.^9,10Arterial spin-labeling (ASL), unlike DSC and dynamic contrast-enhanced perfusion imaging, is a noninvasive MR perfusion technique that uses electromagnetic endogenous arterial water as a freely diffusible tracer instead of an exogenous MR imaging contrast agent. The utility of ASL perfusion imaging in the evaluation of the vascularity of brain tumors has been explored in several recent studies.^11–14 One prior study differentiated hemangioblastomas from metastases on the basis of quantitative blood flow measurements using ASL.¹⁵ The authors reported that tumor blood flow was significantly higher in hemangioblastomas than in metastases. However, their study included a limited number of patients and examined metastatic tumors located primarily in the supratentorial region. Because metastasis usually presents with multiple enhancing supratentorial and infratentorial masses and 90%–95% of hemangioblastomas are in the posterior fossa, it is difficult to differentiate hemangioblastoma from metastasis in patients with only cerebellar masses in daily clinical practice.Therefore, the aim of this study was to determine whether the addition of ASL imaging is useful for differentiating hemangioblastoma from metastasis in a homogeneous cohort of patients with only cerebellar masses and to validate the findings by investigating observer performance.     

Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma

BACKGROUND AND PURPOSE:Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.MATERIALS AND METHODS:Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.RESULTS:Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve > 1.2 μm²/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve < 1.2 μm²/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve > 1.2 μm²/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.CONCLUSIONS:The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve > 1.2 μm²/ms have a survival advantage when treated with bevacizumab.

Malignant gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas, anaplastic mixed oligoastrocytomas, and glioblastoma multiforme (GBM), account for almost 80% of malignant primary brain tumors.¹ GBM, the most aggressive and malignant type of primary brain tumor, has a mean survival of only 12–14 months under the current standard of care of radiotherapy combined with concurrent temozolomide, along with adjuvant temozolomide.^2,3 GBMs are highly vascular tumors, recruiting existing vasculature and generating neovasculature from excessive levels of circulating angiogenic growth factors, including vascular endothelial growth factor (VEGF). The highly vascular nature of these tumors has led to a new class of antiangogenic agents, for which there are many ongoing clinical trials in GBM.^4–6Standard imaging techniques are limited in their ability to evaluate the effectiveness of antiangiogenic therapy in malignant gliomas due to a reduction in contrast enhancement. These limitations have resulted in a surge of more advanced imaging biomarkers aimed at predicting response to therapy, as summarized in various review articles.^7,8 Among these new imaging biomarkers showing promise are diffusion MR imaging techniques,^9–18 including ADC histogram analysis. Previous results have shown that pretreatment ADC histogram analysis performed within the contrast-enhancing tumor regions can stratify patients with recurrent GBM into high- and low-risk groups. When using a double Gaussian mixed model to represent the ADC histogram, previous studies have shown that a lower mean value of the Gaussian curve (ADC_L) results in a significantly shorter progression-free survival (PFS) and overall survival (OS) in both single-institution⁹ and multicenter clinical trial data¹⁹ when evaluating bevacizumab in malignant gliomas. An important question remains as to whether ADC histogram analysis is a predictive biomarker specific to antiangiogenic therapy in recurrent GBM or whether it is a predictive biomarker independent of the particular treatment administered. In the current study, we performed ADC histogram analysis in patients with recurrent GBM from the University of California, Los Angeles (UCLA) treated with bevacizumab and those with recurrent GBM from the University of Toronto treated with a variety of chemotherapies and never exposed to bevacizumab, to determine whether ADC histogram analysis performed before treatment in recurrent GBM is a bevacizumab-specific or treatment-independent biomarker of treatment response.     

Comparison of Multiple Parameters Obtained on 3T Pulsed Arterial Spin-Labeling,Diffusion Tensor Imaging,and MRS and the Ki-67 Labeling Index in Evaluating Glioma Grading

BACKGROUND AND PURPOSE:Pulsed arterial spin-labeling, DTI, and MR spectroscopy provide useful data for tumor evaluation. We evaluated multiple parameters by using these pulse sequences and the Ki-67 labeling index in newly diagnosed supratentorial gliomas.MATERIALS AND METHODS:All 32 patients, with grade II (3 each of diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma), grade III (3 anaplastic astrocytomas, 4 anaplastic oligodendrogliomas, and 1 anaplastic oligoastrocytoma), and grade IV (14 glioblastomas and 1 glioblastoma with an oligodendroglioma component) cases underwent pulsed arterial spin-labeling, DTI, and MR spectroscopy studies by using 3T MR imaging. The following variables were used to compare the tumors: relative cerebral blood flow, fractional anisotropy; ADC tumor/normal ratios; and the Cho/Cr, NAA/Cho, NAA/Cr, and lactate/Cr ratios. A logistic regression and receiver operating characteristic analysis were used to assess parameters with a high sensitivity and specificity to identify the threshold values for separate grading. We compared the Ki-67 index with various MR imaging parameters in tumor specimens.RESULTS:Significant correlations were observed between the Ki-67 index and the mean, maximum, and minimum ADC, Cho/Cr, and lactate/Cr ratios. The receiver operating characteristic analysis showed that the combination of the minimum ADC and Cho/Cr ratios could differentiate low-grade and high-grade gliomas, with a sensitivity and specificity of 87.0% and 88.9%, respectively. The mean and maximum relative cerebral blood flow ratios were used to classify glioblastomas from other-grade astrocytomas, with a sensitivity and specificity of 92.9% and 83.3%, respectively.CONCLUSIONS:Our findings indicate that pulsed arterial spin-labeling, DTI, and MR spectroscopy are useful for predicting glioma grade. Additionally, the parameters obtained on DTI and MR spectroscopy closely correlated with the proliferative potential of gliomas.

Grading gliomas is necessary to determine the appropriate treatment strategy and assess prognosis. Classifying lesions into 4 grades based on histologic analyses requires tumor specimens obtained via biopsy or surgical resection.¹On conventional MR imaging with gadolinium contrast, the presence of FLAIR abnormalities or gadolinium enhancement reveals the appearance of new lesions. Advanced MR imaging, pulsed arterial spin-labeling (PASL), DTI, and MR spectroscopy provide useful data for evaluating tumors preoperatively. The PASL technique allows cerebral blood flow to be measured noninvasively without exogenous contrast agents. The usefulness of perfusion MR imaging with arterial spin-labeling (ASL) for assessing brain tumor angiogenesis and grading gliomas has been evaluated.^2–7 DTI provides information on anisotropy, including fractional anisotropy (FA), and ADC. A recent study investigating DTI of gliomas showed that the FA and ADC tumor/normal tissue ratios are possible indicators of glioma proliferation and/or grading.^8–10 MR spectroscopy is also a noninvasive method that allows the measurement of various metabolites in vivo, such as Cho, Cr, NAA, and the pathologic levels of lactate (Lac), and has been reported useful for investigating gliomas.^11–13 The use of a combination of these noninvasive parameters has been reported to increase the diagnostic accuracy of glioma grading.^{7,9,11,12,14–18} Very few reports describe comparisons of multiple parameters, including the relative cerebral blood flow (rCBF)-measured PASL sequence on 3T MR imaging, and glioma grading. Immunohistologically, the Ki-67 labeling index on histologic examinations is known to correlate with malignancy, and it also functions as a marker of proliferation in gliomas.¹⁹ According to the previous literature, this index is correlated with various advanced MR imaging parameters.^8,20,21In this study, we performed a comparative review of multiple parameters obtained with pulse sequences evaluated by using 3T MR imaging and glioma grading in newly diagnosed patients with glioma. Our purpose was to evaluate whether the parameters provide useful, complementary information and whether this combination of parameters shows the best performance for grading cerebral gliomas. The results of the present study are clinically valuable for evaluating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) and determining the threshold values by analyzing receiver operating characteristic (ROC) curves. Under the same conditions, we evaluated the correlations between various MR imaging parameters and the proliferation marker, the Ki-67 labeling index.     

Variability of Forebrain Commissures in Callosal Agenesis: A Prenatal MR Imaging Study

BACKGROUND AND PURPOSE:Agenesis of the corpus callosum, even when isolated, may be characterized by anatomic variability. The aim of this study was to describe the types of other forebrain commissures in a large cohort of randomly enrolled fetuses with apparently isolated agenesis of the corpus callosum at prenatal MR imaging.MATERIALS AND METHODS:All fetuses with apparent isolated agenesis of the corpus callosum undergoing prenatal MR imaging from 2004 to 2014, were evaluated for the presence of the anterior or a vestigial hippocampal commissure assessed in consensus by 2 pediatric neuroradiologists.RESULTS:Overall, 62 cases of agenesis of the corpus callosum were retrieved from our data base. In 3/62 fetuses (4.8%), no forebrain commissure was visible at prenatal MR imaging, 23/62 fetuses (37.1%) presented with only the anterior commissure, and 20/62 fetuses (32.3%) showed both the anterior commissure and a residual vestigial hippocampal commissure, whereas in the remaining 16/62 fetuses (25.8%), a hybrid structure merging a residual vestigial hippocampal commissure and a rudiment of the corpus callosum body was detectable. Postnatal MR imaging, when available, confirmed prenatal forebrain commissure findings.CONCLUSIONS:Most fetuses with apparent isolated agenesis of the corpus callosum showed at least 1 forebrain commissure at prenatal MR imaging, and approximately half of fetuses also had a second commissure: a vestigial hippocampal commissure or a hybrid made of a hippocampal commissure and a rudimentary corpus callosum body. Whether such variability is the result of different genotypes and whether it may have any impact on the long-term neurodevelopmental outcome remains to be assessed.

The corpus callosum (CC) is the major white matter forebrain commissure. Agenesis of the corpus callosum (ACC) is among the most common congenital brain anomalies, often coexisting with chromosomal or genetic syndromes and other malformations of the central nervous system or extra-CNS location,^1–4 which may negatively impact the neurodevelopmental outcome.^5–7 MR imaging^8,9 has been introduced in prenatal assessment of suspected ACC as a complementary investigation to sonography, due to its high performance in evaluating the fetal brain structures and detecting associated anomalies that may be overlooked at sonography but may impact the final outcome.Both prenatal and postnatal MR imaging may accurately depict the brain features accompanying ACC. For example, the presence or absence of Probst bundles has been extensively addressed in the literature.^10–12 On the contrary, the involvement in ACC of the other forebrain commissures, namely the anterior commissure (AC) and the hippocampal commissure (HC), has been poorly investigated and mainly as sporadic imaging reports in the postnatal setting.^8,13 These postnatal reports did not provide consistent data about how the other forebrain commissures are involved in ACC. These reports are not the result of a random case screening; rather, they are a collection of clinical cases.Consistent visualization of the other forebrain commissures seems feasible at prenatal MR imaging, albeit very poor data are available regarding the forebrain commissures in fetuses with ACC.The aim of this study was to describe the types of other forebrain commissures and to assess their frequency in a large cohort of fetuses with apparent isolated ACC on prenatal MR imaging.     

An MRI Rating Scale for Amyloid-Related Imaging Abnormalities with Edema or Effusion

BACKGROUND AND PURPOSE:Immune therapy against amyloid-β appears to be a promising target in Alzheimer disease. However, a dose-related risk for ARIA on FLAIR images thought to represent parenchymal vasogenic edema or sulcal effusion (termed “ARIA-E”), has been observed in clinical trials. To assess the intensity of ARIA-E presentation, an MR imaging scale that is both reproducible and easily implemented would assist in monitoring and evaluating this adverse event.MATERIALS AND METHODS:On the basis of a review of existing cases from a phase II bapineuzumab study, a scale was constructed with a 6-point score for the 6 regions on each side of the brain (range, 0–60). Scores would be obtained for both parenchymal and sulcal hyperintensities and frequently co-occurring gyral swelling. Inter-rater reliability between 2 neuroradiologists was evaluated in 20 patients, 10 with known ARIA-E and 10 without, by using the intraclass correlation coefficient.RESULTS:The 2 raters had excellent agreement in the identification of ARIA-E cases. A high inter-rater agreement was observed for scores of parenchymal hyperintensity (ICC = 0.83; 95% CI, 48–96) and sulcal hyperintensity (ICC = 0.89; 95% CI, 63–97) and for the combined scores of the 2 ARIA-E findings (ICC = 0.89; 95% CI, 62–97). Gyral swelling scores were observed to have lower inter-rater agreement (ICC = 0.54; 95% CI, −0.06–0.86).CONCLUSIONS:The proposed rating scale provides a reliable and easily implemented instrument to grade ARIA-E imaging findings. We currently do not recommend including swelling.

Alzheimer disease is a progressive neurodegenerative disease associated with dementia and is histopathologically characterized by cerebral neuronal loss, deposits of extracellular plaques of Aβ, and the intraneural accumulation of hyperphosphorylated τ neurofibrillary tangles.^1,2 Treatment strategies targeted against these insults are being investigated; however, to date, no curative treatment exists. Therapies targeting the Aβ plaques have the longest research history, with the first animal models of immunotherapy for AD introduced >10 years ago.³ Several human in vivo trials have been completed or are ongoing using both active and passive immunization strategies for Aβ.^4–6 Immunization against Aβ is hypothesized to lead to an immune-mediated cleavage and removal of Aβ depositions in the brain.⁷ Animal and human in vivo amyloid PET studies have shown that immunization therapy is effective in terms of Aβ removal, and several studies based on active immunization with the full-length Aβ42 peptide suggested clinical benefits.^3,8,9In addition to Aβ removal, MR imaging findings have been observed that are considered likely related to the clearance mechanism.^5,6,10 Dose-related findings include vasogenic edema, sulcal effusion, superficial siderosis, and cerebral microbleeds. The latter are also naturally observed in AD, because lobar microbleeds are related to cerebral amyloid angiopathy and AD pathology.^5,10,11–15 Because both findings are considered related to amyloid pathology, the term “amyloid-related imaging abnormalities” has been proposed. ARIA is further subdivided into ARIA-H, representing hemosiderin deposits or superficial hemosiderosis, and ARIA-E, representing parenchymal vasogenic edema or sulcal effusion. ARIA-E can present with different imaging features, such as gyral swelling and sulcal hyperintensity, along with white matter hyperintensity.¹⁶Scoring guidelines and rating scales for the detection of microbleeds have been established and are widely used in research studies.^15,17 Given the number of clinical trials in patients with AD targeting Aβ, a standardized assessment of this rather new imaging finding of ARIA-E would be useful to improve our understanding of its risk factors and outcomes. The aim of our study, therefore, was to establish a reproducible, clinically applicable, visual MR imaging rating scale for ARIA-E and to examine its internal validity in terms of inter-rater reliability.