Multimodality Imaging of Dementia: Clinical Importance and Role of Integrated Anatomic and Molecular Imaging.

Neurodegenerative diseases are a devastating group of disorders that can be difficult to accurately diagnose. Although these disorders are difficult to manage owing to relatively limited treatment options, an early and correct diagnosis can help with managing symptoms and coping with the later stages of these disease processes. Both anatomic structural imaging and physiologic molecular imaging have evolved to a state in which these neurodegenerative processes can be identified relatively early with high accuracy. To determine the underlying disease, the radiologist should understand the different distributions and pathophysiologic processes involved. High-spatial-resolution MRI allows detection of subtle morphologic changes, as well as potential complications and alternate diagnoses, while molecular imaging allows visualization of altered function or abnormal increased or decreased concentration of disease-specific markers. These methodologies are complementary. Appropriate workup and interpretation of diagnostic studies require an integrated, multimodality, multidisciplinary approach. This article reviews the protocols and findings at MRI and nuclear medicine imaging, including with the use of flurodeoxyglucose, amyloid tracers, and dopaminergic transporter imaging (ioflupane). The pathophysiology of some of the major neurodegenerative processes and their clinical presentations are also reviewed; this information is critical to understand how these imaging modalities work, and it aids in the integration of clinical data to help synthesize a final diagnosis. Radiologists and nuclear medicine physicians aiming to include the evaluation of neurodegenerative diseases in their practice should be aware of and familiar with the multiple imaging modalities available and how using these modalities is essential in the multidisciplinary management of patients with neurodegenerative diseases.©RSNA, 2020.

Phase-Contrast MRI: Physics, Techniques, and Clinical Applications.

With phase-contrast imaging, the MRI signal is used to visualize and quantify velocity. This imaging modality relies on phase data, which are intrinsic to all MRI signals. With use of bipolar gradients, degrees of phase shift are encoded and in turn correlated directly with the velocity of protons. The acquisition of diagnostic-quality images requires selection of the correct imaging plane to ensure accurate measurement and selection of the encoding velocity and thus prevent aliasing and achieve the highest signal-to-noise ratio. Multiple applications of phase-contrast imaging are actively used in clinical practice. One of the most common clinical uses is in cardiac valvular flow imaging, at which the data are used to assess the severity of valvular disease and quantify the shunt fraction. In neurologic imaging, phase-contrast imaging can be used to measure the flow of cerebrospinal fluid. This measurement can aid in the diagnosis and direct management of normal pressure hydrocephalus or be used to evaluate the severity of stenosis, such as that in Chiari I malformations. At vascular analysis, phase-contrast imaging can be used to visualize arterial and venous flow, and this application is used most commonly in the brain. Three-dimensional imaging can yield highly detailed flow data in a technique referred to as four-dimensional flow. A more recently identified application is in MR elastography. Shear waves created by using an impulse device can be velocity encoded, and this velocity is directly proportional to the stiffness of the organ, or the shear modulus. This imaging modality is most commonly used in the liver for evaluation of cirrhosis and steatosis, although research on the assessment of other organs is being performed. Phase-contrast imaging is an important tool in the arsenal of MRI examinations and has many applications. Proper use of phase-contrast imaging requires an understanding of the many practical and technical factors and unique physics principles underlying the technique.©RSNA, 2020.

Recurrent metastatic breast cancer manifesting as pulmonary tumor thrombotic microangiopathy with interstitial pulmonary fibrosis and infarcts: A clinicopathological correlation.

Pulmonary Tumor Thrombotic Microangiopathy (PTTM) is a fatal complication of malignancy characterized by embolization of tumor cells to the pulmonary vasculature leading to a vascular reaction resulting in stenosis and pulmonary hypertension. Because the clinical manifestations of PTTM overlap with those of other entities, premortem diagnosis is challenging. We describe an unusual case of PTTM as the only clinical manifestation of recurrent metastatic breast cancer. A 50 year-old woman presented with hypoxemia and echocardiographic findings consistent with pulmonary hypertension and cor pulmonale. Correlation of premortem pulmonary imaging with autopsy histopathologic findings revealed that ill-defined ground-glass opacities identified on CT angiogram corresponded to areas of cellular interstitial fibrosis and widespread intrapulmonary tumor emboli involving predominantly small-sized arteries with associated florid intimal fibrosis. The radiologic nodularities and scattered peripheral wedge-shaped consolidations corresponded to evolving pulmonary infarcts on histopathology. Although retrospectively, the imaging findings were concordant with a spectrum of increasing severity of tumor embolization and vascular remodeling, the diagnosis of PTTM was not made premortem. PTTM is a rare entity that must be considered in cancer patients with unexplained hypoxemia, pulmonary hypertension and lung opacities on imaging.

Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-κB-dependent pathway.

BACKGROUND: Recent studies suggest that CD80 (also known as B7.1) is expressed on podocytes in minimal-change disease (MCD) and may have a role in mediating proteinuria. CD80 expression is known to be induced by Toll-like receptor (TLR) ligands in dendritic cells. We therefore evaluated the ability of TLR to induce CD80 in human cultured podocytes. METHODS: Conditionally immortalized human podocytes were evaluated for TLR expression. Based on high expression of TLR3, we evaluated the effect of polyinosinic-polycytidylic acid (polyIC), a TLR3 ligand, to induce CD80 expression in vitro. RESULTS: TLR1-6 and 9 messenger RNA (mRNA) were expressed in podocytes. Among TLR ligands 1-9, CD80 mRNA expression was significantly induced by polyIC and lipopolysaccharide (TLR4 ligand) with the greatest stimulation by polyIC (6.8 ± 0.7 times at 6 h, P < 0.001 versus control). PolyIC induced increased expression of Cathepsin L, decreased synaptopodin expression and resulted in actin reorganization which suggested a similar injury pattern as observed with lipopolyssaccharide. PolyIC induced type I and type II interferon signaling, nuclear factor kappa B (NF-κB) activation and the induction of CD80 expression. Knockdown of CD80 protected against actin reorganization and reduced synaptopodin expression in response to polyIC. Dexamethasone, a corticosteroid commonly used to treat MCD, also blocked both basal and polyIC-stimulated CD80 expression, as did inhibition of NF-κB. CONCLUSIONS: Activation of TLR3 on cultured human podocytes induces CD80 expression and phenotypic change via an NF-κB-dependent mechanism and is partially blocked by dexamethasone. These studies provide a mechanism by which viral infections may cause proteinuria.