Content codes:Purpose: To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods:In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 4003 magnification highpower fields with iron-containing macrophages.Results: Ten adults (four male participants [mean age, 65 years 6 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years 6 12 years; age range, 32-65 years]; mean age of all participants, 58 years 6 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P , .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells.Conclusion: MRI measurements of susceptibility, R2*, and R2' (R2* -R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Since surviving patients experience severe neurocognitive disabilities, better and more effective treatments are needed to enhance their quality of life. Casein kinase 2 (CK2) is known to regulate cell growth and survival in multiple cancers; however, the role of CK2 in MB is currently being studied. In this study, we verified the importance of CK2 in MB tumorigenesis and discovered that inhibition of CK2 using the small molecule inhibitor, CX-4945, can sensitize MB cells to a well-known and tolerated chemotherapeutic, temozolomide (TMZ). To study the role of CK2 in MB we modulated CK2 expression in multiple MB cells. Exogenous expression of CK2 enhanced cell growth and tumor growth in mice, while depletion or inhibition of CK2 expression decreased MB tumorigenesis. Treatment with CX-4945 reduced MB growth and increased apoptosis. We conducted a highthroughput screen where 4000 small molecule compounds were analyzed to identify compounds that increased the antitumorigenic properties of CX-4945. TMZ was found to work synergistically with CX-4945 to decrease cell survival and increase apoptosis in MB cells. O-6-methylguanine-DNA methyltransferase (MGMT) activity is directly correlated to TMZ sensitivity. We found that loss of CK2 activity reduced β-catenin expression, a known MGMT regulator, which in turn led to a decrease in MGMT expression and an increased sensitivity to TMZ. Our findings show that CK2 is important for MB maintenance and that treatment with CX-4945 can sensitize MB cells to TMZ treatment.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia that affects older adults in the Western world. Symptomatic nervous system invasion in undiagnosed CLL is rare, poorly understood, challenging to treat, and associated with decreased survival. The average survival of CLL patients with central nervous system (CNS) involvement is 3.79 years as compared to six years in CLL patients without CNS involvement. Autopsy studies demonstrated a high incidence of undiagnosed CLL with CNS involvement, suggesting that CNS involvement is either underdiagnosed or subclinical. Although the most common site of CNS involvement is the leptomeninges, our case demonstrates an extremely rare form of CNS diffuse large B-cell parenchymal involvement in a patient with a concurrent diagnosis of systemic CLL.

Supplemental Figure 2: PCR of C. psittaci. PCR results showing absence of C. psittaci DNA in all analyzed samples. PCR amplification was performed using primers against pmp gene of C. psittaci (lanes 16 -29) and GAPDH as positive control (lane 1 -14). All samples showed amplification of GAPDH suggesting presence of human genomic DNA but showed no band in all corresponding samples using primers against pmp gene. Lane 30 was the positive control for pmp primers where C. psittaci DNA was added to human genomic sample represented in lane 15 and showed successful amplification.

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