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Tissue fusion transcript panel gene coverage (55 genes)

Purpose:The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS).Experimental Design:We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel.Results:Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053).Conclusions:Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

Plasma cell-free DNA (cfDNA) concentration (ng/mL) is correlated with (A), total radiographic tumor burden (contrast-enhancing tumor + T2/FLAIR non-enhancing tumor) and (B), contrast-enhancing tumor burden at the first post-radiation MRI scan in patients with newly diagnosed glioblastoma

We have previously demonstrated an independent association between high levels of plasma circulating cell-free DNA (ccfDNA) concentration and poor survival outcomes in patients with newly diagnosed glioblastoma. Given that somatic mutations are rarely detected in glioblastoma patient plasma, we reasoned that DNA shed by tumor (circulating tumor DNA, ctDNA) was not likely to be a driver of prognostic increases in ccfDNA. To investigate the tissue of origin for this prognostic ccfDNA, we analyzed the plasma ccfDNA methylation signatures of 23 patients with newly diagnosed glioblastoma using the Illumina Infinium EPIC array, a genome-wide DNA methylation technique covering over 850,000 CpG sites. Deconvolution of the ccfDNA methylation signatures based on published reference methylomes revealed an increased proportion of ccfDNA derived from granulocytes in glioblastoma specimens compared to healthy controls (p < 0.0001). Further, this granulocyte proportion was increased in patients with high ccfDNA levels (above median value) compared to patients with low ccfDNA (p = 0.0001). Granulocyte proportion correlated with ccfDNA concentration (Spearman r = 0.64, p = 0.001). The top two gene sets identified by differential methylation analysis followed by gene set enrichment analysis (methylGSA) between high- and low-ccfDNA specimens were “neutrophil activation involved in immune response” (GO:0002283, p = 3.4E-23) and “neutrophil degranulation” (GO:0043312, p = 3.4E-23). Additional analysis of ccfDNA fragment size identified larger fragments ( > 700 bp) as the major source of the prognostic signal (log-rank p = 0.002 for progression-free survival) compared to traditionally sized ccfDNA fragments (50-700 bp, log-rank p = 0.12). Taken together, these data suggest that granulocytes are the primary contributing source of prognostic ccfDNA in glioblastoma. Future studies are needed to determine the mechanism through which granulocyte-derived ccfDNA is associated with clinical outcomes in glioblastoma and to explore related therapeutic opportunities.

Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( > 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.

BACKGROUND Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) tumor microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, here we investigated non-invasive quantitative susceptibility mapping (QSM) and T2* MRI relaxometry to quantify iron as imaging biomarkers for TAMs in adult patients with GBM. METHODS In this prospective study, 21 adult patients with GBM were enrolled between 2016 to 2019. Patients underwent a 3D single echo gradient echo sequence in addition to standard anatomical sequences on a 3 Tesla MRI. QSM images were reconstructed using the morphology-enabled dipole inversion (MEDI) algorithm. In 3 subjects, ex vivo imaging of surgical specimens was performed on a Bruker 9.4 Tesla 8.9 cm vertical bore MR using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated by a pixel-wise monoexponential fitting. Each specimen was stained with hematoxylin and eosin, as well as with CD68, CD86, CD206, and L-Ferritin. RESULTS Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). Moreover, the mean susceptibility significantly correlated with positivity percent for CD68 (ρ=0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ=0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). High mean susceptibility in the necrotic core was associated with inferior PFS (hazard ratio,4.5, p=0.016). CONCLUSION MR Susceptibility Imaging can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.

Immunologically-cold tumors including glioblastoma (GBM) are refractory to checkpoint blockade therapy, largely due to extensive infiltration of immunosuppressive macrophages (Mϕs). Consistent with a pro-tumor role of IL-6 in alternative Mϕs polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mϕs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mϕs. Combination of IL-6 inhibition with CD40 stimulation reverses Mϕ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models, particularly inducing complete regression of GL261 tumors after checkpoint blockade. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting opportunities for GBM and other solid tumors., Glioblastomas are generally resistant to treatment with immune checkpoint inhibitors. Here the authors show that IL6 blockade, in combination with a CD40 agonist, overcomes macrophage-mediated immunosuppression and sensitizes glioblastoma to immune checkpoint blockade in preclinical models.

Elevated levels of choline are generally emphasized as marker of increased cellularity and cell membrane turnover in gliomas. In this study, we investigated the incidence rate of lack of choline/creatine and choline/water elevation in a population of grade I–III gliomas. A cohort of 41 patients with histopathologically confirmed gliomas underwent multi-voxel proton magnetic resonance spectroscopy on a 3 T magnetic resonance system prior to treatment. Peak areas for choline and myoinositol were measured from all voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to creatine and unsuppressed water from each voxel. The average metabolite/creatine and metabolite/water ratios from these voxels were then computed. Similarly, average metabolite ratios were computed from normal brain parenchyma. Gliomas were considered for lack of choline elevation when choline/creatine and choline/water ratios from neoplastic regions were less than those from normal brain parenchyma regions. Six of 41 (14.6%) grade I–III gliomas showed lack of elevation for choline/creatine and choline/water ratios compared to normal brain parenchyma. Four of these six gliomas also demonstrated elevated levels of myoinositol/creatine ratio. All other gliomas ( n = 35) had elevated choline levels from neoplastic regions relative to normal parenchyma. The sensitivity of choline/creatine or choline/water in determining a grade I–III glioma was 85.4%. These findings suggest that a lack of choline/creatine or choline/water elevation may be seen in some gliomas and low choline levels should not prevent us from considering the possibility of a grade I–III glioma.

Rationale and Objectives To determine the metabolic effects of developmental venous anomalies (DVAs) and to correlate those effects with conventional magnetic resonance imaging (MRI) findings. Materials and Methods We conducted a retrospective review of MRI and brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) examinations in subjects with DVAs. Conventional MRI was used to determine DVA number, location, size, and associated parenchymal findings such as atrophy, hemorrhage, cavernoma, capillary telangiectasia, cortical dysplasia/polymicrogyria, and white matter signal abnormality. Qualitative and quantitative measures of relative metabolism in the drainage territory of the DVA were measured on 18F-FDG-PET. Results Fifty-four subjects with 57 DVAs were included in the analysis. 38% were associated with qualitative and quantitative metabolic abnormalities on 18F-FDG-PET, with decreased metabolism in the parenchyma surrounding all but one of these DVAs. DVAs draining gray matter were significantly more likely to be hypometabolic than those draining only white matter, suggesting that the metabolic effects of DVAs may be underestimated on 18F-FDG-PET. Conclusion Altered metabolism is seen in the drainage territory of a significant proportion of DVAs, suggesting that these anomalies are vascular lesions with abnormal physiologic features.

BACKGROUND Accurate differentiation of brain infections from necrotic glioblastomas (GBMs) may not always be possible on morphologic MRI or on diffusion tensor imaging (DTI) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) if these techniques are used independently. PURPOSE To investigate the combined analysis of DTI and DSC-PWI in distinguishing brain injections from necrotic GBMs. STUDY TYPE Retrospective. POPULATION Fourteen patients with brain infections and 21 patients with necrotic GBMs. FIELD STRENGTH/SEQUENCE 3T MRI, DTI, and DSC-PWI. ASSESSMENT Parametric maps of mean diffusivity (MD), fractional anisotropy (FA), coefficient of linear (CL), and planar anisotropy (CP) and leakage corrected cerebral blood volume (CBV) were computed and coregistered with postcontrast T1 -weighted and FLAIR images. All lesions were segmented into the central core and enhancing region. For each region, median values of MD, FA, CL, CP, relative CBV (rCBV), and top 90th percentile of rCBV (rCBVmax ) were measured. STATISTICAL TESTS All parameters from both regions were compared between brain infections and necrotic GBMs using Mann-Whitney tests. Logistic regression analyses were performed to obtain the best model in distinguishing these two conditions. RESULTS From the central core, significantly lower MD (0.90 × 10-3 ± 0.44 × 10-3 mm2 /s vs. 1.66 × 10-3 ± 0.62 × 10-3 mm2 /s, P = 0.001), significantly higher FA (0.15 ± 0.06 vs. 0.09 ± 0.03, P

BACKGROUND AND PURPOSE Hyperintensity on T1-weighted imaging in perilesional vasogenic edema has been reported as a useful sign for differentiating cavernous malformation from other hemorrhagic intra-axial masses. In this study, we investigated the frequency of perilesional hyperintensity on T1-weighted imaging in patients with intra-axial hemorrhagic and nonhemorrhagic brain masses. METHODS The study was performed with the approval of the institutional review board. Magnetic resonance images of 218 patients with 282 intra-axial brain masses (129 metastases, 46 gliomas, 18 primary central nervous system lymphomas [PCNSLs], 25 intracerebral hemorrhages, 50 cavernous malformations, and 14 patients with brain abscesses) were evaluated. The signal intensity in perilesional area was qualitatively evaluated on T1-weighted sequences. In addition, signal intensity in perilesional area was quantitatively measured on T1-weighted sequences and normalized to the contralateral white matter. RESULTS Hyperintensity on T1-weighted imaging in perilesional vasogenic edema was found in 12 (9%) of 129 metastases, 8 (16%) of 50 cavernous malformations, 1 (4%) in 25 nonneoplastic intracerebral hemorrhages, and none of the patients with high-grade glioma, PCNSL, or abscess. All of the lesions with perilesional hyperintensity showed either acute or subacute hemorrhage. Pairwise comparison of qualitative hyperintensity on T1-weighted imaging demonstrated no significant difference between the groups. Perilesional hyperintensity on T1-weighted imaging showed high specificity in both metastasis and cavernous malformation groups (94%). CONCLUSION Perilesional hyperintensity on T1-weighted imaging is not limited to cavernous malformations and frequently evident with melanoma and other hemorrhagic metastasis to the brain. In our experience, it was not seen in high-grade glioma, PCNSL, and brain abscess.

BACKGROUND: Quantitative susceptibility mapping (QSM) uses prior information to reconstruct maps, but prior information may not show pathology and introduce inconsistencies with susceptibility maps, degrade image quality and inadvertently smoothing image features. PURPOSE: To develop a local field data-driven QSM reconstruction that does not depend on spatial edge prior information. STUDY TYPE: Retrospective. SUBJECTS, ANIMAL MODELS: A dataset from 2016 ISMRM QSM Challenge, 11 patients with glioblastoma, a patient with microbleeds and porcine heart. SEQUENCE/FIELD STRENGTH: 3D gradient echo sequence on 3T and 7T scanners. ASSESSMENT: Accuracy was compared to Calculation of Susceptibility through Multiple Orientation Sampling (COSMOS), and several published techniques using region of interest (ROI) measurements, root-mean-squared error (RMSE), structural similarity index metric (SSIM), and high-frequency error norm (HFEN). Numerical ranking and semiquantitative image grading was performed by three expert observers to assess overall image quality (IQ) and image sharpness (IS). STATISTICAL TESTS: Bland–Altman, Friedman test, and Conover multiple comparisons. RESULTS: Loss adaptive dipole inversion (LADI) (β = 0.82, R(2) = 0.96), morphology-enabled dipole inversion (MEDI) (β = 0.91, R(2) = 0.97), and fast nonlinear susceptibility inversion (FANSI) (β = 0.81, R(2) = 0.98) had excellent correlation with COSMOS and no bias was detected (bias = 0.006 ± 0.014, P < 0.05). In glioblastoma patients, LADI showed consistently better performance (IQ(Grade) = 2.6 ± 0.4, IS(Grade) = 2.6 ± 0.3, IQ(Rank) = 3.5 ± 0.4, IS(Rank) = 3.9 ± 0.2) compared with MEDI (IQ(Grade) = 2.1 ± 0.3, IS(Grade) = 2 ± 0.5, IQ(Rank) = 2.4 ± 0.5, IS(Rank) = 2.8 ± 0.2) and FANSI (IQ(Grade) = 2.2 ± 0.5, IS(Grade) = 2 ± 0.4, IQ(Rank) = 2.8 ± 0.3, IS(Rank) = 2.1 ± 0.2). Dark artifact visible near the infarcted region in MEDI (Inf(MEDI) = −0.27 ± 0.06 ppm) was better mitigated by FANSI (Inf(FANSI-TGV) = −0.17 ± 0.05 ppm) and LADI (Inf(LADI) = −0.18 ± 0.05 ppm). CONCLUSION: For neuroimaging applications, LADI preserved image sharpness and fine features in glioblastoma and microbleed patients. LADI performed better at mitigating artifacts in cardiac QSM. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY STAGE: 1

Purpose: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). Experimental Design: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. Results: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). Conclusions: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and carries a dismal prognosis. Significant challenges in the care of patients with GBM include marked vascular heterogeneity and arteriovenous (AV) shunting, which results in tumor hypoxia and inadequate delivery of systemic treatments to reach tumor cells. In this study, we investigated the utility of different MR perfusion techniques to detect and quantify arteriovenous (AV) shunting and tumor hypoxia in patients with GBM. Macrovascular shunting was present in 33% of subjects, with the degree of shunting ranging from (37–60%) using arterial spin labeling perfusion. Among the dynamic susceptibility contrast-enhanced perfusion curve features, there were a strong negative correlation between hypoxia score, DSC perfusion curve recovery slope (r = −0.72, P = 0.018) and angle (r = −0.73, P = 0.015). The results of this study support the possibility of using arterial spin labeling and pattern analysis of dynamic susceptibility contrast-enhanced MR Imaging for evaluation of arteriovenous shunting and tumor hypoxia in glioblastoma.

TO THE EDITOR: We read with great interest the recent article by Filss et al. published in The Journal of Nuclear Medicine ([1][1]). They observed a considerable increase of 18F-FET uptake in 26% of subjects compared with preoperative values adjacent to the resection cavity with subsequent decrease

To determine the metabolic effects of developmental venous anomalies (DVAs) and to correlate those effects with conventional magnetic resonance imaging (MRI) findings.We conducted a retrospective review of MRI and brain 18F-fluorodeoxyglucose positron emission tomography (Fifty-four subjects with 57 DVAs were included in the analysis. 38% were associated with qualitative and quantitative metabolic abnormalities onAltered metabolism is seen in the drainage territory of a significant proportion of DVAs, suggesting that these anomalies are vascular lesions with abnormal physiologic features.

Accurate differentiation of brain infections from necrotic glioblastomas (GBMs) may not always be possible on morphologic MRI or on diffusion tensor imaging (DTI) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) if these techniques are used independently.To investigate the combined analysis of DTI and DSC-PWI in distinguishing brain injections from necrotic GBMs.Retrospective.Fourteen patients with brain infections and 21 patients with necrotic GBMs.3T MRI, DTI, and DSC-PWI.Parametric maps of mean diffusivity (MD), fractional anisotropy (FA), coefficient of linear (CL), and planar anisotropy (CP) and leakage corrected cerebral blood volume (CBV) were computed and coregistered with postcontrast TAll parameters from both regions were compared between brain infections and necrotic GBMs using Mann-Whitney tests. Logistic regression analyses were performed to obtain the best model in distinguishing these two conditions.From the central core, significantly lower MD (0.90 × 10Combined analysis of DTI and DSC-PWI may provide better performance in differentiating brain infections from necrotic GBMs.1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:184-194.

The study by Niibo et al1 showed that detecting hyperemic lesions (HLs) using arterial spin-labeling (ASL) imaging is a reliable method to predict and localize subsequent blood–brain barrier disruption and hemorrhagic transformation. With great interest, we have some concerns about the methodology of the study. In the methodology, an HL was defined “as a visually perceivable increase in the CBF [cerebral blood flow] on ASL maps either within or around the hypoperfused lesion. HLs had to be clearly distinct from vascular structures.” Subsequently, the authors used a region of interest of the HL on ASL maps to calculate the quantitative cerebral blood flow values in HLs. The authors did not describe how they could confidently differentiate HLs especially the ones …

Hyperintensity on T1-weighted imaging in perilesional vasogenic edema has been reported as a useful sign for differentiating cavernous malformation from other hemorrhagic intra-axial masses. In this study, we investigated the frequency of perilesional hyperintensity on T1-weighted imaging in patients with intra-axial hemorrhagic and nonhemorrhagic brain masses.The study was performed with the approval of the institutional review board. Magnetic resonance images of 218 patients with 282 intra-axial brain masses (129 metastases, 46 gliomas, 18 primary central nervous system lymphomas [PCNSLs], 25 intracerebral hemorrhages, 50 cavernous malformations, and 14 patients with brain abscesses) were evaluated. The signal intensity in perilesional area was qualitatively evaluated on T1-weighted sequences. In addition, signal intensity in perilesional area was quantitatively measured on T1-weighted sequences and normalized to the contralateral white matter.Hyperintensity on T1-weighted imaging in perilesional vasogenic edema was found in 12 (9%) of 129 metastases, 8 (16%) of 50 cavernous malformations, 1 (4%) in 25 nonneoplastic intracerebral hemorrhages, and none of the patients with high-grade glioma, PCNSL, or abscess. All of the lesions with perilesional hyperintensity showed either acute or subacute hemorrhage. Pairwise comparison of qualitative hyperintensity on T1-weighted imaging demonstrated no significant difference between the groups. Perilesional hyperintensity on T1-weighted imaging showed high specificity in both metastasis and cavernous malformation groups (94%).Perilesional hyperintensity on T1-weighted imaging is not limited to cavernous malformations and frequently evident with melanoma and other hemorrhagic metastasis to the brain. In our experience, it was not seen in high-grade glioma, PCNSL, and brain abscess.

Radiculopathy from dilated epidural varices is a rarely recognized phenomenon, and engorged varices may mimic a disc herniation, fistula or mass. We report a case of a distended bladder causing reversible pelvic venous congestion and resultant epidural venous plexus engorgement. We show marked engorgement of the epidural venous plexus and crowding of the cauda equina from a markedly distended bladder with resolution of these findings following bladder decompression. Familiarity with this clinical entity is crucial to avoid misdiagnosis and to prevent potential unnecessary surgical intervention.

I read with interest the article by Andre et al [1] titled “Toward Quantifying the Prevalence, Severity, and Cost Associated With Patient Motion During Clinical MR Examinations.” In their article, the authors eloquently demonstrated that motion artifacts represent a frequent cause of image degradation in MRI and impose a significant financial burden on radiology departments. There are some additional points worth mentioning. The authors recommended more investment in research and software packages for motion correction, but it would be interesting to know how often the currently available motion correction sequences and softwares were used in the study. Some motion correction techniques, such as PROPELLER, have been shown to be very useful in clinical settings, are available on the majority of imaging platforms [2], and are commonly used in moving patients. Another example is the echo-planar imaging fluid-attenuated inversion recovery sequence, which has shown to produce qualitative and quantitative results comparable with those obtained using conventional fluid-attenuated inversion recovery imaging in the

Background Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. Objective To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Methods Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. Results CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Conclusion Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.

BackgroundCerebral aneurysm formation is one of the cerebrovascular complications of sickle cell disease.ObjectiveTo report the clinical and imaging findings of intracerebral aneurysms and their treatment in pediatric and adult patients with sickle cell disease.MethodsReview of clinical data via chart abstraction and radiologic features at the University of Pennsylvania and Children's Hospital of Philadelphia from 2000 to 2014 and review of the literature since 1942.ResultsNineteen patients with aneurysms (2.7%) were found in 709 imaged patients, including 1.2% of imaged children and 10.8% of adults. A total of 44 aneurysms were detected (52.6% with multiple aneurysms, overall 2.3 per patient), 35 (79.5%) in the anterior circulation and 9 in the posterior circulation (20.4%). Thirty-eight unruptured aneurysms ranging in size from 2 to 6 mm and six ruptured aneurysms ranging in size from 3 to 9 mm in diameter were found. Of the patients with ruptured aneurysms, two were treated by stent-assisted coiling, two by clipping, and one patient with coiling. In the group without a rupture, one patient was treated by coil embolization and one patient with a peripheral middle cerebral artery aneurysm was treated by aneurysmectomy. Three pediatric patients with a previously normal MR angiogram demonstrated new aneurysm formation during the study.ConclusionsAdult patients with sickle cell disease have a high prevalence of aneurysm formation. Both pediatric and adult patients with sickle cell disease tend to develop multiple aneurysms with frequent involvement of atypical locations, in both anterior and posterior circulations.

Optic nerve sheath meningioma is most often discovered in adults and is relatively rare in children. We report a 12-year-old girl with an atypical primary optic nerve meningioma, which demonstrated restricted diffusion on magnetic resonance imaging and high Ki67 labeling index. The patient developed recurrence, despite aggressive surgical resection of primary tumor and local radiation. We are unaware of previous reports documenting this constellation of imaging and histopathologic findings.

We read with interest the recent NeuroImage presented by Ye et al.1 as an example of calcified otogenic brain abscess. The authors described a patient with a 2-year history of recurrent episodes of purulent discharge from the left ear and an incidental calcified brain mass in the ipsilateral temporal lobe.1 In the largest case series of calcifying pseudoneoplasm of the neuraxis (CAPNON), all …