The tauopathies: Neuroimaging characteristics and emerging experimental therapies.

The tauopathies are a heterogeneous group of neurodegenerative disorders in which the prevailing underlying disease process is intracellular deposition of abnormal misfolded tau protein. Diseases often categorized as tauopathies include progressive supranuclear palsy, chronic traumatic encephalopathy, corticobasal degeneration, and frontotemporal lobar degeneration. Tauopathies can be classified through clinical assessment, imaging findings, histologic validation, or molecular biomarkers tied to the underlying disease mechanism. Many tauopathies vary in their clinical presentation and overlap substantially in presentation, making clinical diagnosis of a specific primary tauopathy difficult. Anatomic imaging findings are also rarely specific to a single tauopathy, and when present may not manifest until well after the point at which therapy may be most impactful. Molecular biomarkers hold the most promise for patient care and form a platform upon which emerging diagnostic and therapeutic applications could be developed. One of the most exciting developments utilizing these molecular biomarkers for assessment of tau deposition within the brain is tau-PET imaging utilizing novel ligands that specifically target tau protein. This review will discuss the background, significance, and clinical presentation of each tauopathy with additional attention to the pathologic mechanisms at the protein level. The imaging characteristics will be outlined with select examples of emerging imaging techniques. Finally, current treatment options and emerging therapies will be discussed. This is by no means a comprehensive review of the literature but is instead intended for the practicing radiologist as an overview of a rapidly evolving topic.

Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat Model-Protocol Development.

The fate of intranasal aerosolized radiolabeled polymeric micellar nanoparticles (LPNPs) was tracked with positron emission tomography/computer tomography (PET/CT) imaging in a rat model to measure nose-to-brain delivery. A quantitative temporal and spatial testing protocol for new radio-nanotheranostic agents was sought in vivo. LPNPs labeled with a zirconium 89 (89Zr) PET tracer were administered via intranasal or intravenous delivery, followed by serial PET/CT imaging. After 2 h of continuous imaging, the animals were sacrificed, and the brain substructures (olfactory bulb, forebrain, and brainstem) were isolated. The activity in each brain region was measured for comparison with the corresponding PET/CT region of interest via activity measurements. Serial imaging of the LPNPs (100 nm PLA-PEG-DSPE+89Zr) delivered intranasally via nasal tubing demonstrated increased activity in the brain after 1 and 2 h following intranasal drug delivery (INDD) compared to intravenous administration, which correlated with ex vivo gamma counting and autoradiography. Although assessment of delivery from nose to brain is a promising approach, the technology has several limitations that require further development. An experimental protocol for aerosolized intranasal delivery is presented herein, which may provide a platform for better targeting the olfactory epithelium.

Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors.

PURPOSE OF REVIEW: This review will explore the latest in advanced imaging techniques, with a focus on the complementary nature of multiparametric, multimodality imaging using magnetic resonance imaging (MRI) and positron emission tomography (PET). RECENT FINDINGS: Advanced MRI techniques including perfusion-weighted imaging (PWI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI), and MR chemical exchange saturation transfer (CEST) offer significant advantages over conventional MR imaging when evaluating tumor extent, predicting grade, and assessing treatment response. PET performed in addition to advanced MRI provides complementary information regarding tumor metabolic properties, particularly when performed simultaneously. 18F-fluoroethyltyrosine (FET) PET improves the specificity of tumor diagnosis and evaluation of post-treatment changes. Incorporation of radiogenomics and machine learning methods further improve advanced imaging. The complementary nature of combining advanced imaging techniques across modalities for brain tumor imaging and incorporating technologies such as radiogenomics has the potential to reshape the landscape in neuro-oncology.

Sensitivity of Thoracic Digital Tomosynthesis (DTS) for the Identification of Lung Nodules.

Thoracic computed tomography (CT) is considered the gold standard for detection lung pathology, yet its efficacy as a screening tool in regards to cost and radiation dose continues to evolve. Chest radiography (CXR) remains a useful and ubiquitous tool for detection and characterization of pulmonary pathology, but reduced sensitivity and specificity compared to CT. This prospective, blinded study compares the sensitivity of digital tomosynthesis (DTS), to that of CT and CXR for the identification and characterization of lung nodules. Ninety-five outpatients received a posteroanterior (PA) and lateral CXR, DTS, and chest CT at one care episode. The CXR and DTS studies were independently interpreted by three thoracic radiologists. The CT studies were used as the gold standard and read by a fourth thoracic radiologist. Nodules were characterized by presence, location, size, and composition. The agreement between observers and the effective radiation dose for each modality was objectively calculated. One hundred forty-five nodules of greatest diameter larger than 4 mm and 215 nodules less than 4 mm were identified by CT. DTS identified significantly more >4 mm nodules than CXR (DTS 32 % vs. CXR 17 %). CXR and DTS showed no significant difference in the ability to identify the smaller nodules or central nodules within 3 cm of the hilum. DTS outperformed CXR in identifying pleural nodules and those nodules located greater than 3 cm from the hilum. Average radiation dose for CXR, DTS, and CT were 0.10, 0.21, and 6.8 mSv, respectively. Thoracic digital tomosynthesis requires significantly less radiation dose than CT and nearly doubles the sensitivity of that of CXR for the identification of lung nodules greater than 4 mm. However, sensitivity and specificity for detection and characterization of lung nodules remains substantially less than CT. The apparent benefits over CXR, low cost, rapid acquisition, and minimal radiation dose of thoracic DTS suggest that it may be a useful procedure. Work-up of a newly diagnosed nodule will likely require CT, given its superior cross-sectional characterization. Further investigation of DTS as a diagnostic, screening, and surveillance tool is warranted.