MRI and PET of Brain Tumor Neuroinflammation in the Era of Immunotherapy, From the AJR Special Series on Inflammation.

With the emergence of immune-modulating therapies, brain tumors present important diagnostic imaging challenges. These challenges include planning personalized treatment and adjudicating accurate monitoring approaches and therapeutically specific response criteria. The challenges have been due, in part reliance on nonspecific imaging metrics, such as gadolinium contrast-enhanced MRI or FDG PET, and rapidly evolving biologic understanding of neuroinflammation. The importance of the tumor immune interaction and ability to therapeutically augment inflammation to improve clinical outcomes make it necessary for radiologists to develop a working knowledge of the immune system and its role in clinical neuroimaging. The purpose of this article is to review relevant biologic concepts of the tumor microenvironment of primary and metastatic brain tumors, the interactions between the tumors and the immune system, and MRI and PET methods for imaging inflammatory elements associated with these malignancies. In recognition of the growing fields of immunotherapeutics and precision oncology, clinically translatable imaging metrics for the diagnosis and monitoring of brain tumor neuroinflammation are highlighted. Practical guidance is provided for implementing iron nanoparticle imaging, including imaging indications, protocols, interpretation, and pitfalls. A comprehensive understanding of the inflammatory mechanisms within brain tumors and their imaging features will facilitate the development of innovative noninvasive prognostic and predictive imaging strategies for precision oncology.

Ferumoxytol-Enhanced MRI Is Not Inferior to Gadolinium-Enhanced MRI in Detecting Intracranial Metastatic Disease and Metastasis Size.

OBJECTIVE. The goal of this intraindividual comparison study was to investigate whether ferumoxytol-enhanced MRI is as effective as standard-of-care gadolinium-enhanced MRI in detecting intracranial metastatic disease. MATERIALS AND METHODS. We retrospectively reviewed all patients who underwent imaging as part of two ongoing ferumoxytol-enhanced and gadolinium-enhanced MRI protocol studies to compare the number and size of enhancing metastatic lesions. Two neuroradiologists independently measured enhancing metastases on ferumoxytol-enhanced MR images and on control gadolinium-enhanced MR images. The number and size of metastases were compared on an intraindividual basis. Primary diagnoses were recorded. A linear mixed-effects model was used to compare differences in cubic root of volume between gadolinium-enhanced and ferumoxytol-enhanced MRI. A signed rank test was used to evaluate differences between reviewers. RESULTS. MR images from 19 patients with brain metastases were analyzed (seven with lung cancer, three with breast cancer, three with melanoma, two with ovarian cancer, one with colon cancer, one with renal cell carcinoma, one with carcinoid tumor, and one with uterine cancer). Reviewer 1 identified 77 masses on ferumoxytol-enhanced MRI and 72 masses on gadolinium-enhanced MRI. Reviewer 2 identified 83 masses on ferumoxytol-enhanced MRI and 78 masses on gadolinium-enhanced MRI. For reviewer 1, ferumoxytol-enhanced MRI showed a mean tumor size measuring 1.1 mm larger in each plane compared with gadolinium-enhanced MRI (p = 0.1887). For reviewer 2, ferumoxytol-enhanced MRI showed a mean tumor size measuring 1.0 mm larger in each plane (p = 0.2892). No significant differences in number of metastases or tumor sizes were observed between contrast agents or reviewers. CONCLUSION. Intracranial metastatic disease detection with ferumoxytol-enhanced MRI was not inferior to detection with gadolinium-enhanced MRI. Ferumoxytol-enhanced MRI could improve workup and monitoring of patients with brain metastases if gadolinium-enhanced MRI is contraindicated.

Quantitative comparison of delayed ferumoxytol T1 enhancement with immediate gadoteridol enhancement in high grade gliomas.

PURPOSE: Delayed ferumoxytol enhancement on T1 -weighted images appears visually similar to gadoteridol enhancement. The purpose of this study was to quantitatively compare ferumoxytol T1 enhancement to gadoteridol enhancement with an objective, semi-automated method. METHODS: 206 sets of post-gadoteridol and 24 h post-ferumoxytol T1 -weighted scans from 58 high grade glioma patients were analyzed (9 pre-chemoradiation, 111 < 90 days post-chemoradiation, 21 > 90 days post-chemoradiation, 65 post-bevacizumab scans). Enhancement volumes and signal intensities normalized to normal appearing tissue proximal to enhancement were calculated with a semi-automated method. Enhancement cube root volumes (D) and signal intensities (SI) were compared between the 2 contrast agents, and relative difference of D and SI were compared in different treatment groups with multivariate analysis. Within patient differences in D and SI before and after treatment with bevacizumab or steroid were assessed in 26 patients in each treatment group. RESULTS: When compared to gadoteridol, ferumoxytol D was 13.83% smaller and SI was 7.24% lower (P < 0.0001). The relative differences in D and SI between the 2 contrast agents were not significantly different between treatment groups (P > 0.05). Relative difference in D and SI did not change significantly in response to bevacizumab (P = 0.5234 and P = 0.2442, respectively) or to steroid (P = 0.3774, P = 0.0741) in the within patient comparison. CONCLUSION: The correlation between the 2 contrast agents' enhancement size and signal intensity and their similar behavior in response to therapy suggest that ferumoxytol can be used for revealing enhancement in high grade glioma patients. Magn Reson Med 80:224-230, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

[Potential health risks from consumption of water with arsenic in Colima, Mexico]. / Riesgos potenciales de salud por consumo de agua con arsénico en Colima, México.

OBJECTIVE:: To estimate potential health risks due to chronic ingestion of arsenic from groundwater in Colima, Mexico. MATERIALS AND METHODS:: Samples were randomly taken in 36 wells from 10 local aquifers. Analysis was performed by ICP-OES following international standards. Geostatistical interpolation was performed with ArcGIS, implementing a model weighting inverse distance to estimate arsenic routes of exposure and consumption on each locality. The Hazard Quotient Ratio (HQ) and carcinogenic risk (R) for As were estimated. RESULTS:: The weighted average HQ for arsenic in Colima is 2.41. There are HQ> 1 values indicating adverse non-cancer health effects by continuous and prolonged intake of water with arsenic, which could affect 183 832 individuals in the state. The risk of developing any type of cancer among the population in this study due to high arsenic concentrations in groundwater (R) is 1.089E-3, which could statistically cause 446 cases of cancer. CONCLUSIONS:: Current levels of arsenic in groundwater increase carcinogenic and non-carcinogenic human health risks in Colima.

CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma.

Establishing the diagnosis of focal brain lesions in patients with unexplained neurologic symptoms represents a challenge. The goal of this study is to provide evidence supporting functional roles for CXC chemokine ligand (CXCL)13 and interleukin (IL)-10 in central nervous system (CNS) lymphomas and to evaluate the utility of each as prognostic and diagnostic biomarkers. We demonstrate for the first time that elevated CXCL13 concentration in cerebrospinal fluid (CSF) is prognostic and that CXCL13 and CXCL12 mediate chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. Expression of the activated form of Janus kinase 1 supported a role for IL-10 in prosurvival signaling. We determined the concentration of CXCL13 and IL-10 in CSF of CNS lymphoma patients and control cohorts including inflammatory and degenerative neurologic disease in a multicenter study involving 220 patients. Bivariate elevated CXCL13 plus IL-10 was 99.3% specific for primary and secondary CNS lymphoma, with sensitivity significantly greater than reference standard CSF tests. These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration.

Performance of Apparent Diffusion Coefficient Values and Conventional MRI Features in Differentiating Tumefactive Demyelinating Lesions From Primary Brain Neoplasms.

OBJECTIVE: Tumefactive demyelinating lesions (TDLs) remain one of the most common brain lesions to mimic a brain tumor, particularly primary CNS lymphoma (PCNSL) and high-grade gliomas. The purpose of our study was to evaluate the ability of apparent diffusion coefficient (ADC) values and conventional MRI features to differentiate TDLs from PCNSLs and high-grade gliomas. MATERIALS AND METHODS: Seventy-five patients (24 patients with TDLs, 28 with PCNSLs, and 23 with high-grade gliomas) with 168 brain lesions (70 TDLs, 68 PCNSLs, and 30 high-grade gliomas) who underwent DWI before surgery or therapy were included in the study. Minimum ADC (ADC(min)) and average ADC (ADC(avg)) values were calculated for each lesion. ANOVA and ROC analyses were performed. ROC analyses were also performed for the presence of incomplete rim enhancement and for the number of lesions. Multiple-variable logistic regression with ROC analysis was then performed to evaluate performance in multiple-variable models. RESULTS: ADC(min) was statistically significantly higher (p < 0.01) in TDLs (mean, 0.886; 95% CI, 0.802-0.931) than in PCNSLs (0.547; 95% CI, 0.496-0.598) and high-grade gliomas (0.470; 95% CI, 0.385-0.555). (All ADC values in this article are reported in units of × 10(-3) mm(2)/s.) ADC(avg) was statistically significantly higher (p < 0.01) in TDLs (mean, 1.362; 95% CI, 1.268-1.456) than in PCNSLs (0.990; 95% CI, 0.919-1.061) but not in high-grade gliomas (1.216; 95% CI, 1.074-1.356). Multiple-variable models showed statistically significant individual effects and superior diagnostic performance on ROC analysis. CONCLUSION: TDLs can be diagnosed on preoperative MRI with a high degree of specificity; MRI features of incomplete rim enhancement, high ADC values, and a large number of lesions individually increase the probability and diagnostic confidence that a lesion is a TDL.

Apparent diffusion coefficient in glioblastoma with PNET-like components, a GBM variant.

Glioblastoma (GBM) with primitive neuroectodermal tumor (PNET)-like (GBM-PNET) components is a rare variant of GBM. Recent studies describe PNET-like clinical behavior in these patients-with significantly increased propensity for CSF dissemination and a benefit of "PNET-like" chemotherapy. The imaging appearance of GBM-PNET is not well-described and given areas of marked cellularity in the PNET components one might expect significantly reduced diffusion on MRI. The purpose of this study is to quantitatively evaluate the diffusion characteristics in GBM-PNET and compare them with conventional GBMs. Nine patients with surgical specimens yielding GBM-PNET were identified from the UCSF Pathology files. MR images of these patients were reviewed retrospectively. DWI (diffusion-weighted imaging) sequences were analyzed with multiple regions of interests placed within the tumor, and ADC (apparent diffusion coefficient) values were measured. Results were compared to previously published ADC values in pathology-proven conventional GBM cases from our institution. Reduced ADC was seen in GBM-PNET (mean 581 × 10(-6) mm(2)/s, range 338-817) compared to previously published mean of 1,030 × 10(-6) mm(2)/s in the enhancing components of conventional GBMs. We report substantially reduced ADC values in GBM-PNETs compared to conventional GBMs. If demonstrated in a larger sample, when areas of marked reduced diffusion are seen in a suspected GBM, MRI may appropriately direct tissue sampling and can advocate a thorough search for PNET-like components on histopathology. These patients may have a higher chance of developing CSF dissemination and may benefit from "PNET-like" platinum-based chemotherapy.

Prevalence and significance of perivascular soft tissue surrounding the hepatic artery after liver transplantation.

OBJECTIVE: The objective of this study was to determine the prevalence and significance of perivascular soft tissue surrounding the hepatic artery on computed tomography (CT) after liver transplantation. MATERIALS AND METHODS: A total of 119 consecutive patients who underwent liver transplantation were retrospectively identified from a search of electronic medical records. Fourteen patients had histologic proof of posttransplant lymphoproliferative disease (PTLD). For each patient, the initial CT scan after transplantation, and the most recent CT scan if available, was analyzed for the presence of soft tissue in the porta hepatis region, particularly surrounding the transplanted hepatic artery. The hepatic artery was identified, and the maximum diameter of the soft tissue surrounding the vessel was measured and classified using the following scale: grade 0, none; grade 1, mild; grade 2, moderate; grade 3, moderate-large; and grade 4, large. RESULTS: Prevalence of perivascular soft tissue was 93% in the initial CT scans and follow-up studies. Comparing the initial and follow-up soft tissue measurements, 34% decreased, 62% were unchanged, and 4% increased. Using the Fisher exact test and a Mann-Whitney test, there was no statistically significant difference in the prevalence or diameter of perivascular soft tissue when comparing patients with pathologically proven PTLD and patients with no PTLD. Twenty-nine of the 119 patients underwent 68 positron emission tomography/CT scans in the time interval analyzed. Ninety percent of these patients had no abnormal fluorodeoxyglucose activity in the porta hepatis and portacaval regions. CONCLUSIONS: The presence of isolated perivascular soft tissue in patients after liver transplantation is a common finding and is not associated with lymphoproliferative disease.

Imaging Genomics of Glioma Revisited: Analytic Methods to Understand Spatial and Temporal Heterogeneity.

An improved understanding of the cellular and molecular biologic processes responsible for brain tumor development, growth, and resistance to therapy is fundamental to improving clinical outcomes. Imaging genomics is the study of the relationships between microscopic, genetic, and molecular biologic features and macroscopic imaging features. Imaging genomics is beginning to shift clinical paradigms for diagnosing and treating brain tumors. This article provides an overview of imaging genomics in gliomas, in which imaging data including hallmarks such as IDH-mutation, MGMT methylation, and EGFR-mutation status can provide critical insights into the pretreatment and posttreatment stages. This article will accomplish the following: 1) review the methods used in imaging genomics, including visual analysis, quantitative analysis, and radiomics analysis; 2) recommend suitable analytic methods for imaging genomics according to biologic characteristics; 3) discuss the clinical applicability of imaging genomics; and 4) introduce subregional tumor habitat analysis with the goal of guiding future radiogenetics research endeavors toward translation into critically needed clinical applications.

Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Incorporating Supramaximal Resection into Survival Stratification of IDH-Wildtype Glioblastoma: A Refined Multi-institutional Recursive Partitioning Analysis.

PURPOSE: To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections. EXPERIMENTAL DESIGN: This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared to a previous RTOG RPA model. RESULTS: In the developmental cohort, the RPA model included age, MGMTp methylation status, KPS, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis (class I: median overall survival [OS] 57.3 months), while low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared to the previous RTOG RPA model. CONCLUSIONS: The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups.

Exploring Heavy Metal and Metalloid Exposure in Children: A Pilot Biomonitoring Study near a Sugarcane Mill.

Sugarcane production has been linked to the release of heavy metals and metalloids (HM/MTs) into the environment, raising concerns about potential health risks. This study aimed to assess the levels of 19 HM/MTs in children living near a sugarcane mill through a pilot biomonitoring investigation. We investigated sex-related differences in these element levels and their correlations. A cross-sectional study was conducted, analyzing data from 20 children in the latter part of 2023. Spearman correlation coefficients with 95% confidence intervals (CIs) were used to assess the relationships between urinary HM/MT levels. Detectable levels of 17 out of the 19 HM/MTs were found across the entire study sample, with arsenic and copper detectable in 95% of the children. Titanium exhibited higher levels in boys compared to girls (p = 0.017). We identified 56 statistically significant correlations, with 51 of them being positive, while the remaining coefficients indicated negative relationships. This study characterized HM/MT levels in school-aged children residing near a sugarcane mill through a pilot biomonitoring investigation. Further research employing larger sample sizes and longitudinal assessments would enhance our understanding of the dynamics and health impacts of HM/MT exposure in this vulnerable population.

Multiparametric magnetic resonance imaging discerns glioblastoma immune microenvironmental heterogeneity.

RATIONALE AND OBJECTIVE: Poor clinical outcomes for patients with glioblastoma are in part due to dysfunction of the tumor-immune microenvironment. An imaging approach able to characterize immune microenvironmental signatures could provide a framework for biologically based patient stratification and response assessment. We hypothesized spatially distinct gene expression networks can be distinguished by multiparametric Magnetic Resonance Imaging (MRI) phenotypes. MATERIALS AND METHODS: Patients with newly diagnosed glioblastoma underwent image-guided tissue sampling allowing for co-registration of MRI metrics with gene expression profiles. MRI phenotypes based on gadolinium contrast enhancing lesion (CEL) and non-enhancing lesion (NCEL) regions were subdivided based on imaging parameters (relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC)). Gene set enrichment analysis and immune cell type abundance was estimated using CIBERSORT methodology. Significance thresholds were set at a p-value cutoff 0.005 and an FDR q-value cutoff of 0.1. RESULTS: Thirteen patients (eight men, five women, mean age 58 ± 11 years) provided 30 tissue samples (16 CEL and 14 NCEL). Six non-neoplastic gliosis samples differentiated astrocyte repair from tumor associated gene expression. MRI phenotypes displayed extensive transcriptional variance reflecting biological networks, including multiple immune pathways. CEL regions demonstrated higher immunologic signature expression than NCEL, while NCEL regions demonstrated stronger immune signature expression levels than gliotic non-tumor brain. Incorporation of rCBV and ADC metrics identified sample clusters with differing immune microenvironmental signatures. CONCLUSION: Taken together, our study demonstrates that MRI phenotypes provide an approach for non-invasively characterizing tumoral and immune microenvironmental glioblastoma gene expression networks.

Multi-modality imaging assessment of microbubbles and cerebral emboli in left ventricular pulsed field ablation.

BACKGROUND: Pulsed field ablation (PFA) may have a superior safety profile compared to other technologies, but it has the potential to cause gaseous microbubbles (MB), which may be associated with cerebral emboli. Limited relative safety data has been published regarding PFA in the left ventricle (LV). METHODS: Healthy and chronic myocardial infarction (MI) swine underwent PFA (monopolar, biphasic, 25 Amps) in the LV using an irrigated focal catheter under intra-cardiac echocardiography (ICE) guidance for MB monitoring. Two control swine received air MBs through the lumen of the ablation catheter. Swine underwent brain MRI before and after PFA (or control air MB injection). Gross pathology and histology of brains with abnormal MRI findings were performed. RESULTS: Four healthy and 5 chronic MI swine underwent 124 left ventricular PFA applications. No PFA-related MB formation was noted on ICE. Both control swine developed multiple acute emboli in the thalamus and caudate on DWI, ADC, and FLAIR brain MRI images in response to air MB injection. Of the 9 PFA swine, there were no abnormalities on ADC or FLAIR images. There was one hyperintense focus in the left putamen on the DWI trace image, but the absence of ADC or FLAIR affirmation suggested it was artifact. Gross pathology and histopathology of this region did not detect any abnormalities. CONCLUSIONS: Focal monopolar biphasic PFA of both healthy and chronically infarcted left ventricular myocardium does not generate any MB or cerebral emboli observable on ICE and brain MRI.

Mismatch repair-deficient glioma with spatially distinct IDH-mutant and IDH-wild type components arising in the setting of Lynch syndrome.

Pathogenic mutations in MLH1, MSH2, PMS2, and MSH6 compromise DNA mismatch repair mechanisms and in the heterozygous state result in Lynch syndrome, which is typified by a predisposition to endometrial, ovarian, colorectal, gastric, breast, hematologic, and soft tissue cancers. Rarely, germline pathogenic aberrations in these genes are associated with the development of primary central nervous system tumors. We present a report of an adult female with no prior cancer history who presented with a multicentric, infiltrative supratentorial glioma involving both the left anterior temporal horn and left precentral gyrus. Surgical treatment and neuropathological/molecular evaluation of these lesions revealed discordant isocitrate dehydrogenase (IDH) status and histologic grade at these spatially distinct disease sites. A frameshift alteration within the MLH1 gene (p.R217fs*12, c.648delT) was identified in both lesions and subsequently identified in germline testing of a blood sample, consistent with Lynch syndrome. Despite distinct histopathologic features and divergent IDH status of the patient's tumors, the molecular findings suggest that both sites of intracranial neoplasia may have developed as a consequence of underlying monoallelic germline mismatch repair deficiency. This case illustrates the importance of characterizing the genetic profile of multicentric gliomas and highlights the oncogenic potential of germline mismatch repair gene pathogenic alterations within central nervous system gliomas.

Revealing the biology behind MRI signatures in high grade glioma.

Magnetic resonance imaging (MRI) measurements are routinely collected during the treatment of high-grade gliomas (HGGs) to characterize tumor boundaries and guide surgical tumor resection. Using spatially matched MRI and transcriptomics we discovered HGG tumor biology captured by MRI measurements. We strategically overlaid the spatially matched omics characterizations onto a pre-existing transcriptional map of glioblastoma multiforme (GBM) to enhance the robustness of our analyses. We discovered that T1+C measurements, designed to capture vasculature and blood brain barrier (BBB) breakdown and subsequent contrast extravasation, also indirectly reveal immune cell infiltration. The disruption of the vasculature and BBB within the tumor creates a permissive infiltrative environment that enables the transmigration of anti-inflammatory macrophages into tumors. These relationships were validated through histology and enrichment of genes associated with immune cell transmigration and proliferation. Additionally, T2-weighted (T2W) and mean diffusivity (MD) measurements were associated with angiogenesis and validated using histology and enrichment of genes involved in neovascularization. Furthermore, we establish an unbiased approach for identifying additional linkages between MRI measurements and tumor biology in future studies, particularly with the integration of novel MRI techniques. Lastly, we illustrated how noninvasive MRI can be used to map HGG biology spatially across a tumor, and this provides a platform to develop diagnostics, prognostics, or treatment efficacy biomarkers to improve patient outcomes.

Deciphering spatially distinct immune microenvironments in glioblastoma using ferumoxytol and gadolinium-enhanced and FLAIR hyperintense MRI phenotypes.

Background: MRI with gadolinium (Gd)-contrast agents is used to assess glioblastoma treatment response but does not specifically reveal heterogeneous biology or immune microenvironmental composition. Ferumoxytol (Fe) contrast is an iron nanoparticle that localizes glioblastoma macrophages and microglia. Therefore, we hypothesized that the use of Fe contrast improves upon standard Gd-based T1-weighted and T2/FLAIR analysis by specifically delineating immune processes. Methods: In this, HIPAA-compliant institutional review board-approved prospective study, stereotactic biopsy samples were acquired from patients with treatment-naïve and recurrent glioblastoma based on MR imaging phenotypes; Gd and Fe T1 enhancement (Gd+, Fe+) or not (Gd-, Fe-), as well as T2-Flair hyperintensity (FLAIR+, FLAIR-). Analysis of genetic expression was performed with RNA microarrays. Imaging and genomic expression patterns were compared using false discovery rate statistics. Results: MR imaging phenotypes defined a variety of immune pathways and Hallmark gene sets. Gene set enrichment analysis demonstrated that Gd+, Fe+, and FLAIR+ features were individually correlated with the same 7 immune process gene sets. Fe+ tissue showed the greatest degree of immune Hallmark gene sets compared to Gd+ or Flair+ tissues and had statistically elevated M2 polarized macrophages, among others. Importantly, the FLAIR+ Gd+ and Fe- imaging phenotypes did not demonstrate expression of immune Hallmark gene sets. Conclusions: Our study demonstrates the potential of Fe and Gd-enhanced MRI phenotypes to reveal spatially distinct immune processes within glioblastoma. Fe improves upon the standard of care Gd enhancement by specifically localizing glioblastoma-associated inflammatory processes, providing valuable insights into tumor biology.

Pancreatic imaging mimics: part 1, imaging mimics of pancreatic adenocarcinoma.

OBJECTIVE: The purpose of this article is to describe the imaging features of diseases that may closely simulate pancreatic adenocarcinoma, either radiologically or pathologically. CONCLUSION: Neoplastic and inflammatory diseases that can closely simulate pancreatic adenocarcinoma include neuroendocrine tumor, metastasis to the pancreas, lymphoma, groove pancreatitis, autoimmune pancreatitis, and focal chronic pancreatitis. Atypical imaging findings that should suggest diagnoses other than adenocarcinoma include the absence of significant duct dilatation, incidental detection, hypervascularity, large size (> 5 cm), IV tumor thrombus, and intralesional ducts or cysts.

Intracranial subdural osteoma: a rare benign tumor that can be differentiated from other calcified intracranial lesions utilizing MR imaging.

We report the magnetic resonance (MR) imaging characteristics of subdural osteoma and other benign calcified intracranial lesions to highlight imaging features that differentiate between these disease entities. A 63-year-old woman presented with progressively altered mental status. Non-contrast CT demonstrated a densely calcified right middle cranial fossa extra-axial mass. MR imaging of the lesion demonstrated T1 and T2 hypointensity without evidence of contrast enhancement, parenchymal abnormality, or connection to adjacent venous structures. Diffusion weighted imaging demonstrated markedly decreased signal intensity and artificially reduced diffusion on apparent diffusion coefficient map. Histologically, the tumor was predominantly composed of lamellar bone and small fragments of residual dura consistent with subdural osteoma. This case demonstrates that radiological examination can provide additional insight into the origin of intracranial osteomas (extradural versus subdural versus sinonasal) and help distinguish from other diagnostic considerations including benign meningeal ossification and calcified meningioma prior to surgical resection.