Debra Horng

Rapid 3D phenotyping of cardiovascular development in mouse embryos by micro-CT with iodine staining.

Background—Microcomputed tomography (micro-CT) has been used extensively in research to generate high-resolution 3D images of calcified tissues in small animals nondestructively. It has been especially useful for the characterization of skeletal mutations but limited in its utility for the analysis of soft tissue such as the cardiovascular system. Visualization of the cardiovascular system has been largely restricted to structures that can be filled with radiopaque intravascular contrast agents in adult animals. Recent ex vivo studies using osmium tetroxide, iodinated contrast agents, inorganic iodine, and phosphotungstic acid have demonstrated the ability to stain soft tissues differentially, allowing for high intertissue contrast in micro-CT images. In the present study, we demonstrate the application of this technology for visualization of cardiovascular structures in developing mouse embryos using Lugol solution (aqueous potassium iodide plus iodine). Methods and Results—We show the optimization of this method to obtain ex vivo micro-CT images of embryonic and neonatal mice with excellent soft-tissue contrast. We demonstrate the utility of this method to visualize key structures during cardiovascular development at various stages of embryogenesis. Our method benefits from the ease of sample preparation, low toxicity, and low cost. Furthermore, we show how multiple cardiac defects can be demonstrated by micro-CT in a single specimen with a known genetic lesion. Indeed, a previously undescribed cardiac venous abnormality is revealed in a PlexinD1 mutant mouse. Conclusions—Micro-CT of iodine-stained tissue is a valuable technique for the characterization of cardiovascular development and defects in mouse models of congenital heart disease.

Comparison of R2* correction methods for accurate fat quantification in fatty liver

To compare the performance of fat fraction quantification using single‐R2* and dual‐R2* correction methods in patients with fatty liver, using MR spectroscopy (MRS) as the reference standard.

Quantitative susceptibility mapping in the abdomen as an imaging biomarker of hepatic iron overload

Purpose: The purpose of this work was to develop and demonstrate feasibility and initial clinical validation of quantitative susceptibility mapping (QSM) in the abdomen as an imaging biomarker of hepatic iron overload. Theory and Methods: In general, QSM is faced with the challenges of background field removal and dipole inversion. Respiratory motion, the presence of fat, and severe iron overload further complicate QSM in the abdomen. We propose a technique for QSM in the abdomen that addresses these challenges. Data were acquired from 10 subjects without hepatic iron overload and 33 subjects with known or suspected iron overload. The proposed technique was used to estimate the susceptibility map in the abdomen, from which hepatic iron overload was measured. As a reference, spin‐echo data were acquired for R2‐based LIC estimation. Liver R2* was measured for correlation with liver susceptibility estimates. Results: Correlation between susceptibility and R2‐based LIC estimation was R2 = 0.76 at 1.5 Tesla (T) and R2 = 0.83 at 3T. Furthermore, high correlation between liver susceptibility and liver R2* (R2 = 0.94 at 1.5T; R2 = 0.93 at 3T) was observed. Conclusion: We have developed and demonstrated initial validation of QSM in the abdomen as an imaging biomarker of hepatic iron overload. Magn Reson Med 74:673–683, 2015.

Micro–Computed Tomography Measurements of Peripheral Lung Pathology in Chronic Obstructive Pulmonary Disease

BACKGROUND The smaller airways, < 2 mm in diameter, offer little resistance in normal lungs, but become the major site of obstruction in chronic obstructive pulmonary disease (COPD). OBJECTIVE To examine bronchiolar remodeling and alveolar destruction in COPD using micro-computed tomography (micro-CT). METHODS Micro-CT was used to measure the number and cross-sectional lumen area of terminal bronchioles (TB) and alveolar mean linear intercept (Lm) in 4 lungs removed from patients with very severe (GOLD-4) COPD and 4 unused donor lungs that served as controls. These lungs were inflated with air to a transpulmonary pressure (P(L)) of 30 cm H(2)O and held at P(L) 10 cm H(2)O while they were frozen solid in liquid nitrogen vapor. A high resolution CT scan was performed on the frozen specimen prior to cutting it into 2-cm thick transverse slices. Representative core samples of lung tissue 2 cm long and 1 cm in diameter cut from each slice were fixed at -80 degrees C in a 1% solution of gluteraldehyde in pure acetone, post-fixed in osmium, critically point dried, and examined by micro-CT. RESULTS A 10-fold reduction in terminal bronchiolar number and a 100-fold reduction in their minimal cross-sectional lumen area were measured in both emphysematous and non-emphysematous regions of the COPD lungs. CONCLUSIONS The centrilobular emphysematous phenotype of COPD is associated with narrowing and obliteration of the terminal bronchioles that begins prior to the onset of emphysematous destruction.

Validation of MRI biomarkers of hepatic steatosis in the presence of iron overload in the ob/ob mouse.

To validate the utility and performance of a T  2* correction method for hepatic fat quantification in an animal model of both steatosis and iron overload.

Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature

Stroke is the third leading cause of death and a significant contributor of morbidity in the United States. In humans, suboptimal cerebral collateral circulation within the circle of Willis (CW) predisposes to ischemia and stroke risk in the setting of occlusive carotid artery disease. Unique genes or developmental pathways responsible for proper CW formation are unknown. Herein we characterize a mouse model lacking Notch signaling in vascular smooth muscle cells (vSMCs), in which the animals are intolerant to reduced cerebral blood flow. Remarkably, unilateral carotid artery ligation results in profound neurological sequelae and death. After carotid ligation, perfusion of the ipsilateral cerebral hemisphere was markedly diminished, suggesting an anastomotic deficiency within the CW. High-resolution microcomputed tomographic (μ-CT) imaging revealed profound defects in cerebrovascular patterning, including interruption of the CW and anatomic deformity of the cerebral arteries. These data identify a vSMC-autonomous function for Notch signaling in patterning and collateral formation within the cerebral arterial circulation. The data further implicate genetic or functional deficiencies in Notch signaling in the pathogenesis of anatomic derangements underlying cerebrovascular accidents.

High‐spatial and high‐temporal resolution dynamic contrast‐enhanced perfusion imaging of the liver with time‐resolved three‐dimensional radial MRI

Detection, characterization, and monitoring the treatment of hepatocellular carcinomas (HCC) in patients with cirrhosis is challenging because of their variable and rapid arterial enhancement. Multiphase dynamic contrast‐enhanced MRI is used clinically for HCC assessment; however, the method suffers from limited temporal resolution and difficulty in coordinating imaging and breath‐hold timing within a narrow temporal window of interest. In this article, a volumetric, high‐spatial resolution, and high‐temporal resolution dynamic contrast‐enhanced liver imaging method for improved detection and characterization of HCC is demonstrated.

Improving chemical shift encoded water–fat separation using object-based information of the magnetic field inhomogeneity

The purpose of this work was to improve the robustness of existing chemical shift encoded water–fat separation methods by incorporating object‐based information of the B0 field inhomogeneity.

Quantification of liver fat in the presence of iron overload.

To evaluate the accuracy of R2* models (1/T2* = R2*) for chemical shift‐encoded magnetic resonance imaging (CSE‐MRI)‐based proton density fat‐fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard.

Quantitative hepatic perfusion modeling using DCE-MRI with sequential breathholds.

To develop and demonstrate the feasibility of a new formulation for quantitative perfusion modeling in the liver using interrupted DCE‐MRI data acquired during multiple sequential breathholds.