Prognostication of overall survival in patients with brain metastases using diffusion tensor imaging and dynamic susceptibility contrast-enhanced MRI.

OBJECTIVES: To investigate the prognostic utility of DTI and DSC-PWI perfusion-derived parameters in brain metastases patients. METHODS: Retrospective analyses of DTI-derived parameters (MD, FA, CL, CP, and CS) and DSC-perfusion PWI-derived rCBVmax from 101 patients diagnosed with brain metastases prior to treatment were performed. Using semi-automated segmentation, DTI metrics and rCBVmax were quantified from enhancing areas of the dominant metastatic lesion. For each metric, patients were classified as short- and long-term survivors based on analysis of the best coefficient for each parameter and percentile to separate the groups. Kaplan-Meier analysis was used to compare mOS between these groups. Multivariate survival analysis was subsequently conducted. A correlative histopathologic analysis was performed in a subcohort (n = 10) with DTI metrics and rCBVmax on opposite ends of the spectrum. RESULTS: Significant differences in mOS were observed for MDmin (p < 0.05), FA (p < 0.01), CL (p < 0.05), and CP (p < 0.01) and trend toward significance for rCBVmax (p = 0.07) between the two risk groups, in the univariate analysis. On multivariate analysis, the best predictive survival model was comprised of MDmin (p = 0.05), rCBVmax (p < 0.05), RPA (p < 0.0001), and number of lesions (p = 0.07). On histopathology, metastatic tumors showed significant differences in the amount of stroma depending on the combination of DTI metrics and rCBVmax values. Patients with high stromal content demonstrated poorer mOS. CONCLUSION: Pretreatment DTI-derived parameters, notably MDmin and rCBVmax, are promising imaging markers for prognostication of OS in patients with brain metastases. Stromal cellularity may be a contributing factor to these differences. ADVANCES IN KNOWLEDGE: The correlation of DTI-derived metrics and perfusion MRI with patient outcomes has not been investigated in patients with treatment naïve brain metastasis. DTI and DSC-PWI can aid in therapeutic decision-making by providing additional clinical guidance.

Astrocyte activation imaging with 11C-acetate and amyloid PET in mild cognitive impairment due to Alzheimer pathology.

BACKGROUND: Neuroinflammation is a well-known feature of early Alzheimer disease (AD) yet astrocyte activation has not been extensively evaluated with in vivo imaging in mild cognitive impairment (MCI) due to amyloid plaque pathology. Unlike neurons, astrocytes metabolize acetate, which has potential as a glial biomarker in neurodegeneration in response to AD pathologic features. Since the medial temporal lobe (MTL) is a hotspot for AD neurodegeneration and inflammation, we assessed astrocyte activity in the MTL and compared it to amyloid and cognition. METHODS: We evaluate spatial patterns of in vivo astrocyte activation and their relationships to amyloid deposition and cognition in a cross-sectional pilot study of six participants with MCI and five cognitively normal participants. We measure 11C-acetate and 18F-florbetaben amyloid standardized uptake values ratios (SUVRs) and kinetic flux compared to the cerebellum on PET, with MRI and neurocognitive testing. RESULTS: MTL 11C-acetate SUVR was significantly elevated in MCI compared to cognitively normal participants (P = 0.03; Cohen d = 1.76). Moreover, MTL 11C-acetate SUVR displayed significant associations with global and regional amyloid burden in MCI. Greater MTL 11C-acetate retention was significantly related with worse neurocognitive measures including the Montreal Cognitive Assessment (P = 0.001), word list recall memory (P = 0.03), Boston naming test (P = 0.04) and trails B test (P = 0.04). CONCLUSIONS: While further validation is required, this exploratory pilot study suggests a potential role for 11C-acetate PET as a neuroinflammatory biomarker in MCI and early AD to provide clinical and translational insights into astrocyte activation as a pathological response to amyloid.

Does the application of diffusion weighted imaging improve the prediction of survival in patients with resected brain metastases? A retrospective multicenter study.

BACKGROUND: Brain metastases are common in clinical practice. Many clinical scales exist for predicting survival and hence deciding on best treatment but none are individualised and none use quantitative imaging parameters. A multicenter study was carried out to evaluate the prognostic utility of a simple diffusion weighted MRI parameter, tumor apparent diffusion coefficient (ADC). METHODS: A retrospective analysis of imaging and clinical data was performed on a cohort of 223 adult patients over a ten-year period 2002-2012 pooled from three institutions. All patients underwent surgical resection with histologically confirmed brain metastases and received adjuvant whole brain radiotherapy and/or chemotherapy. Survival was modelled using standard clinical variables and statistically compared with and without the addition of tumor ADC. RESULTS: The median overall survival was 9.6 months (95% CI 7.5-11.7) for this cohort. Greater age (p = 0.002), worse performance status (p < 0.0001) and uncontrolled extracranial disease (p < 0.0001) were all significantly associated with shorter survival in univariate analysis. Adjuvant whole brain radiotherapy (p = 0.007) and higher tumor ADC (p < 0.001) were associated with prolonged survival. Combining values of tumor ADC with conventional clinical scoring systems such as the Graded Prognostic Assessment (GPA) score significantly improved the modelling of survival (e.g. concordance increased from 0.5956 to 0.6277 with Akaike's Information Criterion reduced from 1335 to 1324). CONCLUSIONS: Combining advanced MRI readings such as tumor ADC with clinical scoring systems is a potentially simple method for improving and individualising the estimation of survival in patients having surgery for brain metastases.

Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema.

OBJECTIVE: Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP. METHODS: Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension. RESULTS: Reduced pituitary gland height was moderately sensitive for IIH WP (80%) but had low specificity (64%). Increased optic nerve sheath diameter was less sensitive (51%) and only moderately specific (83%). Flattening of the posterior globe was highly specific (97%) but had low sensitivity (57%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100% specific, while maintaining a sensitivity of 64%. Of patients with CH + EOP, 30% had 3 or more MRI features, suggesting IIH WOP in those patients. CONCLUSION: A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.

Incidental Orbital Neuroendocrine Metastases on 111In-OctreoScan and MRI.

Neuroendocrine tumors have a propensity to metastasize, but rarely to the orbits. A 69-year-old woman with history of neuroendocrine tumor of pancreatic primary underwent routine follow-up In-pentetreotide (OctreoScan) imaging, with 24-hour whole-body planar images showing subtle right periorbital tracer uptake that localized to extraocular muscles on subsequent SPECT/CT. Orbital MRI further defined the location of these highly suspicious orbital metastases, which were treated with external radiation, with follow-up MRI showing decreased size of the orbital metastases. Early identification and treatment of orbital metastases is critical to help preserve vision and quality of life.

18F-Flortaucipir PET/MRI Correlations in Nonamnestic and Amnestic Variants of Alzheimer Disease.

Nonamnestic Alzheimer disease (AD) variants, including posterior cortical atrophy and the logopenic variant of primary progressive aphasia, differ from amnestic AD in distributions of tau aggregates and neurodegeneration. We evaluated whether 18F-flortaucipir (also called 18F-AV-1451) PET, targeting tau aggregates, detects these differences, and we compared the results with MRI measures of gray matter (GM) atrophy. Methods: Five subjects with posterior cortical atrophy, 4 subjects with the logopenic variant of primary progressive aphasia, 6 age-matched patients with AD, and 6 control subjects underwent 18F-flortaucipir PET and MRI. SUV ratios and GM volumes were compared using regional and voxel-based methods. Results: The subgroups showed the expected 18F-flortaucipir-binding patterns. Group effect sizes were generally stronger with 18F-flortaucipir PET than with MRI volumes. There were moderate-to-high correlations between regional GM atrophy and 18F-flortaucipir uptake. 18F-flortaucipir binding and GM atrophy correlated similarly to cognitive test performance. Conclusion:18F-flortaucipir binding corresponds to the expected neurodegeneration patterns in nonamnestic AD, with potential for earlier detection of pathology than is possible with MRI atrophy measures.

PET-Computed Tomography in Head and Neck Cancer: Current Evidence and Future Directions.

Head and neck cancers are among the most common cancers worldwide. More than 90% to 95% are squamous cell carcinomas (SCCs). Accurate staging at diagnosis optimizes treatment planning with improved outcomes. Recently, 18F-fluorodeoxyglucose (FDG) PET-computed tomography (CT) has shown tremendous value at diagnosis for accurate staging, treatment planning, and prognostication; and after definitive therapy for assessing response and long-term surveillance. Novel non-FDG PET tracers are under investigation, which have great potential for improving patient care in this era of personalized medicine.

Elevated FDG Activity in the Nonpneumatized Sphenoid Bone in an Infant.

A 7-month-old boy with malignant rhabdoid tumor of the right lateral neck, status post resection and chemotherapy, underwent FDG PET/CT for restaging. The images showed diffuse increased activity in the spleen and in the bone marrow of the appendicular bones and the spine, which is related to hematopoietin administered after chemotherapy. The images also revealed intense activity in the region of sphenoid bone, which is not a common region to have elevated FDG activity. The subsequent MRI scan showed that this activity was due to not-yet-converted red marrow in the sphenoid bone in this pediatric patient.

Wallerian Degeneration Beyond the Corticospinal Tracts: Conventional and Advanced MRI Findings.

Wallerian degeneration (WD) is defined as progressive anterograde disintegration of axons and accompanying demyelination after an injury to the proximal axon or cell body. Since the 1980s and 1990s, conventional magnetic resonance imaging (MRI) sequences have been shown to be sensitive to changes of WD in the subacute to chronic phases. More recently, advanced MRI techniques, such as diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI), have demonstrated some of earliest changes attributed to acute WD, typically on the order of days. In addition, there is increasing evidence on the value of advanced MRI techniques in providing important prognostic information related to WD. This article reviews the utility of conventional and advanced MRI techniques for assessing WD, by focusing not only on the corticospinal tract but also other neural tracts less commonly thought of, including corticopontocerebellar tract, dentate-rubro-olivary pathway, posterior column of the spinal cord, corpus callosum, limbic circuit, and optic pathway. The basic anatomy of these neural pathways will be discussed, followed by a comprehensive review of existing literature supported by instructive clinical examples. The goal of this review is for readers to become more familiar with both conventional and advanced MRI findings of WD involving important neural pathways, as well as to illustrate increasing utility of advanced MRI techniques in providing important prognostic information for various pathologies.

Role of Ultrasound in Complications of Hematopoetic Stem Cell Transplantation.

Hematopoetic stem cell transplantation (HSCT) is an established therapeutic option for both malignant and nonmalignant indications, whose incidence has continued to increase in recent years. Because of its lower cost and lack of radiation exposure, ultrasound examination is often the first-line imaging modality in evaluating patients both before and after HSCT. It is important for radiologists to be aware of sonographic manifestations of the complications that may arise from HSCT. In this study, we will review the basics of HSCT, the role of imaging, and ultrasound examination findings in common and uncommon complications arising from HSCT.

Capricorn-A Web-Based Automatic Case Log and Volume Analytics for Diagnostic Radiology Residents.

RATIONALE AND OBJECTIVES: On-service clinical learning is a mainstay of radiology education. However, an accurate and timely case log is difficult to keep, especially in the absence of software tools tailored to resident education. Furthermore, volume-related feedback from the residency program sometimes occurs months after a rotation ends, limiting the opportunity for meaningful intervention. MATERIALS AND METHODS: We surveyed the residents of a single academic institution to evaluate the current state of and the existing need for tracking interpretation volume. Using the results of the survey, we created an open-source automated case log software. Finally, we evaluated the effect of the software tool on the residency in a 1-month, postimplementation survey. RESULTS: Before implementation of the system, 89% of respondents stated that volume is an important component of training, but 71% stated that volume data was inconvenient to obtain. Although the residency program provides semiannual reviews, 90% preferred reviewing interpretation volumes at least once monthly. After implementation, 95% of the respondents stated that the software is convenient to access, 75% found it useful, and 88% stated they would use the software at least once a month. The included analytics module, which benchmarks the user using historical aggregate average volumes, is the most often used feature of the software. Server log demonstrates that, on average, residents use the system approximately twice a week. CONCLUSIONS: An automated case log software system may fulfill a previously unmet need in diagnostic radiology training, making accurate and timely review of volume-related performance analytics a convenient process.

Intracellular uptake and trafficking of difluoroboron dibenzoylmethane-polylactide nanoparticles in HeLa cells.

In this study, nanoparticles based on difluoroboron dibenzoylmethane-poly(lactic acid) (BF(2)dbmPLA) are prepared. Polylactic acid or polylactide is a commonly used degradable polymer, while the boron dye possesses a large extinction coefficient, high emission quantum yield, two-photon absorption, and sensitivity to the surrounding environment. BF(2)dbmPLA exhibits molecular-weight-dependent emission properties and can be formulated as stable nanoparticles, suggesting that its unique optical properties may be useful in multiple contexts for probing intracellular environments. Here we show that BF(2)dbmPLA nanoparticles are internalized into cultured HeLa cells by endocytosis, and that within the cellular milieu, they retain their fluorescence properties. BF(2)dbmPLA nanoparticles are photostable, resisting laser-induced photobleaching under conditions that destroy the fluorescence of a common photostable probe, LysoTracker Blue. Their endocytosis is also lipid-raft-dependent, as evidenced by their significant colocalization with cholera toxin B subunit in membrane compartments after uptake and their sensitivity of uptake to methyl-beta-cyclodextrin. Additionally, BF(2)dbmPLA nanoparticle endocytosis utilizes microtubules and actin filaments. Internalized BF(2)dbmPLA nanoparticles do not accumulate in acidic late endosomes and lysosomes but within a perinuclear nonlysosomal compartment. These findings demonstrate the feasibility of using novel BF(2)dbmPLA nanoparticles exhibiting diverse emission properties for in situ, live cell imaging and suggest that their endogenous uptake occurs through a lipid-raft-dependent endocytosis mechanism.