Quantitative CT Scoring for Local COPD Severity.

Chronic obstructive pulmonary disease (COPD) is complex, and its course is difficult to predict due to its diverse pathophysiology. Small airway disease (SAD), a key component of COPD and potential target for emerging therapeutics, may be reversible in mild COPD, but left unchecked, may worsen, leading to airway loss and emphysema. The dual nature of SAD complicates clinical management of COPD patients, necessitating more accurate monitoring methods.

Local heterogeneity of normal lung parenchyma and small airways disease are associated with COPD severity and progression.

Background: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline.

Topologic Parametric Response Mapping Identifies Tissue Subtypes Associated with Emphysema Progression.

Rationale And Objectives: Small airways disease (SAD) and emphysema are significant components of chronic obstructive pulmonary disease (COPD), a heterogenous disease where predicting progression is difficult. SAD, a principal cause of airflow obstruction in mild COPD, has been identified as a precursor to emphysema. Parametric Response Mapping (PRM) of chest computed tomography (CT) can help distinguish SAD from emphysema.

Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression.

Objectives: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline.

Quantitative CT Correlates with Local Inflammation in Lung of Patients with Subtypes of Chronic Lung Allograft Dysfunction.

Chronic rejection of lung allografts has two major subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), which present radiologically either as air trapping with small airways disease or with persistent pleuroparenchymal opacities. Parametric response mapping (PRM), a computed tomography (CT) methodology, has been demonstrated as an objective readout of BOS and RAS and bears prognostic importance, but has yet to be correlated to biological measures. Using a topological technique, we evaluate the distribution and arrangement of PRM-derived classifications of pulmonary abnormalities from lung transplant recipients undergoing redo-transplantation for end-stage BOS (N = 6) or RAS (N = 6).

Improved detection of air trapping on expiratory computed tomography using deep learning.

Background: Radiologic evidence of air trapping (AT) on expiratory computed tomography (CT) scans is associated with early pulmonary dysfunction in patients with cystic fibrosis (CF). However, standard techniques for quantitative assessment of AT are highly variable, resulting in limited efficacy for monitoring disease progression.

Objective: To investigate the effectiveness of a convolutional neural network (CNN) model for quantifying and monitoring AT, and to compare it with other quantitative AT measures obtained from threshold-based techniques.

Parametric Response Mapping of FLAIR MRI Provides an Early Indication of Progression Risk in Glioblastoma.

Rationale And Objectives: Glioblastoma image evaluation utilizes Magnetic Resonance Imaging contrast-enhanced, T1-weighted, and noncontrast T2-weighted fluid-attenuated inversion recovery (FLAIR) acquisitions. Disease progression assessment relies on changes in tumor diameter, which correlate poorly with survival. To improve treatment monitoring in glioblastoma, we investigated serial voxel-wise comparison of anatomically-aligned FLAIR signal as an early predictor of GBM progression.

Influence of Inspiratory/Expiratory CT Registration on Quantitative Air Trapping.

Rationale And Objectives: The aim of this study was to assess variability in quantitative air trapping (QAT) measurements derived from spatially aligned expiration CT scans.

Materials And Methods: Sixty-four paired CT examinations, from 16 school-age cystic fibrosis subjects examined at four separate time intervals, were used in this study. For each pair, visually inspected lobe segmentation maps were generated and expiration CT data were registered to the inspiration CT frame.

Multimodal imaging provides insight into targeted therapy response in metastatic prostate cancer to the bone.

Metastatic prostate cancer to bone remains incurable, driving efforts to develop individualized, targeted therapies to improve clinical outcomes while limiting adverse side-effects. Due to the complexity in cellular signaling pathways and the interaction between cancer and its microenvironment, multiparametric imaging approaches for treatment response may improve understanding of the biological effects of therapy. An orthotopic model of castration resistant prostate cancer (CRPC) bone metastasis was treated with the tyrosine kinase inhibitor Cabozantinib (CABO).

Vascular Deformation Mapping (VDM) of Thoracic Aortic Enlargement in Aneurysmal Disease and Dissection.

Thoracic aortic aneurysm is a common and lethal disease that requires regular imaging surveillance to determine timing of surgical repair and prevent major complications such as rupture. Current cross-sectional imaging surveillance techniques, largely based on computed tomography angiography, are focused on measurement of maximal aortic diameter, although this approach is limited to fixed anatomic positions and is prone to significant measurement error. Here we present preliminary results showing the feasibility of a novel technique for assessing change in aortic dimensions, termed vascular deformation mapping (VDM).

CT-Based Local Distribution Metric Improves Characterization of COPD.

Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD). Although promising, large variability in the standard method for analyzing PRM has been observed. We postulate that representing the 3D PRM data as a single scalar quantity (relative volume of PRM) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes.

Semiautomated Workflow for Clinically Streamlined Glioma Parametric Response Mapping.

Management of glioblastoma multiforme remains a challenging problem despite recent advances in targeted therapies. Timely assessment of therapeutic agents is hindered by the lack of standard quantitative imaging protocols for determining targeted response. Clinical response assessment for brain tumors is determined by volumetric changes assessed at 10 weeks post-treatment initiation.

A Pilot Study of Quantitative MRI Parametric Response Mapping of Bone Marrow Fat for Treatment Assessment in Myelofibrosis.

Myelofibrosis (MF) is a hematologic neoplasm arising as a primary disease or secondary to other myeloproliferative neoplasms (MPNs). Both primary and secondary MF are uniquely associated with progressive bone marrow fibrosis, displacing normal hematopoietic cells from the marrow space and disrupting normal production of mature blood cells. Activation of the JAK2 signaling pathway in hematopoietic stem cells commonly causes MF, and ruxolitinib, a drug targeting this pathway, is the treatment of choice for many patients.

Potential for Early Fracture Risk Assessment in Patients with Metastatic Bone Disease using Parametric Response Mapping of CT Images.

Pathologic vertebral compression fractures (PVCF) cause significant morbidity in patients with bone metastases from breast cancer and other malignancies. Due to limitations of existing biochemical and imaging biomarkers, clinicians currently have no reliable metrics to identify patients with impending PVCF, impeding efforts to prevent this severe complication. To establish the feasibility of a new method for defining risk of PVCF, we retrospectively analyzed serial CT scans from five breast cancer patients using parametric response mapping (PRM) to quantify dynamic bone density changes that preceded an event.

The Impact of Sources of Variability on Parametric Response Mapping of Lung CT Scans.

Parametric response mapping (PRM) of inspiration and expiration computed tomography (CT) images improves the radiological phenotyping of chronic obstructive pulmonary disease (COPD). PRM classifies individual voxels of lung parenchyma as normal, emphysematous, or nonemphysematous air trapping. In this study, bias and noise characteristics of the PRM methodology to CT and clinical procedures were evaluated to determine best practices for this quantitative technique.

Development of a Multiparametric Voxel-Based Magnetic Resonance Imaging Biomarker for Early Cancer Therapeutic Response Assessment.

Quantitative magnetic resonance imaging (MRI)-based biomarkers, which capture physiological and functional tumor processes, were evaluated as imaging surrogates of early tumor response following chemoradiotherapy in glioma patients. A multiparametric extension of a voxel-based analysis, referred as the parametric response map (PRM), was applied to quantitative MRI maps to test the predictive potential of this metric for detecting response. Fifty-six subjects with newly diagnosed high-grade gliomas treated with radiation and concurrent temozolomide were enrolled in a single-site prospective institutional review board-approved MRI study.

Apparent diffusion coefficient is highly reproducible on preclinical imaging systems: Evidence from a seven-center multivendor study.

Purpose: To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems.

Materials And Methods: A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.

Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable.

Phosphorylation of FADD by the kinase CK1α promotes KRASG12D-induced lung cancer.

Genomic amplification of the gene encoding and phosphorylation of the protein FADD (Fas-associated death domain) is associated with poor clinical outcome in lung cancer and in head and neck cancer. Activating mutations in the guanosine triphosphatase RAS promotes cell proliferation in various cancers. Increased abundance of phosphorylated FADD in patient-derived tumor samples predicts poor clinical outcome.

Parametric response mapping monitors temporal changes on lung CT scans in the subpopulations and intermediate outcome measures in COPD Study (SPIROMICS).

Rationale And Objectives: The longitudinal relationship between regional air trapping and emphysema remains unexplored. We have sought to demonstrate the utility of parametric response mapping (PRM), a computed tomography (CT)-based biomarker, for monitoring regional disease progression in chronic obstructive pulmonary disease (COPD) patients, linking expiratory- and inspiratory-based CT metrics over time.

Materials And Methods: Inspiratory and expiratory lung CT scans were acquired from 89 COPD subjects with varying Global Initiative for Chronic Obstructive Lung Disease (GOLD) status at 30 days (n = 13) or 1 year (n = 76) from baseline as part of the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) clinical trial.

Image registration for quantitative parametric response mapping of cancer treatment response.

Imaging biomarkers capable of early quantification of tumor response to therapy would provide an opportunity to individualize patient care. Image registration of longitudinal scans provides a method of detecting treatment associated changes within heterogeneous tumors by monitoring alterations in the quantitative value of individual voxels over time, which is unattainable by traditional volumetric-based histogram methods. The concepts involved in the use of image registration for tracking and quantifying breast cancer treatment response using parametric response mapping (PRM), a voxel-based analysis of diffusion-weighted magnetic resonance imaging (DW-MRI) scans, are presented.

Imaging proteolytic activity in live cells and animal models.

In addition to their degradative role in protein turnover, proteases play a key role as positive or negative regulators of signal transduction pathways and therefore their dysregulation contributes to many disease states. Regulatory roles of proteases include their hormone-like role in triggering G protein-coupled signaling (Protease-Activated-Receptors); their role in shedding of ligands such as EGF, Notch and Fas; and their role in signaling events that lead to apoptotic cell death. Dysregulated activation of apoptosis by the caspase family of proteases has been linked to diseases such as cancer, autoimmunity and inflammation.

Multimodality imaging of tumor and bone response in a mouse model of bony metastasis.

Cancer drug development generally performs in vivo evaluation of treatment effects that have traditionally relied on detection of morphologic changes. The emergence of new targeted therapies, which may not result in gross morphologic changes, has spurred investigation into more specific imaging methods to quantify response, such as targeted fluorescent probes and bioluminescent cells. The present study investigated tissue response to docetaxel or zoledronic acid (ZA) in a mouse model of bony metastasis.