Cristian Badea

Overview:

Dr. Cristian T. Badea is a Professor in the Department of Radiology and faculty in the Departments of Biomedical Engineering and Medical Physics. His research focuses on pre-clinical imaging. Dr. Badea has research interests in the physics and biomedical applications of computed tomography (CT), micro-CT, tomosynthesis, and image reconstruction algorithms.


Positions:

Professor in Radiology

Radiology
School of Medicine

Associate Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2001

University of Patras (Greece)

Grants:

Tumor perfusion in small animals with tomographic digital subtraction angiography

Administered By
Radiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

MRI-Based Deep Learning Segmentation and Radiomics of Sarcoma in Mice.

Small-animal imaging is an essential tool that provides noninvasive, longitudinal insight into novel cancer therapies. However, considerable variability in image analysis techniques can lead to inconsistent results. We have developed quantitative imaging for application in the preclinical arm of a coclinical trial by using a genetically engineered mouse model of soft tissue sarcoma. Magnetic resonance imaging (MRI) images were acquired 1 day before and 1 week after radiation therapy. After the second MRI, the primary tumor was surgically removed by amputating the tumor-bearing hind limb, and mice were followed for up to 6 months. An automatic analysis pipeline was used for multicontrast MRI data using a convolutional neural network for tumor segmentation followed by radiomics analysis. We then calculated radiomics features for the tumor, the peritumoral area, and the 2 combined. The first radiomics analysis focused on features most indicative of radiation therapy effects; the second radiomics analysis looked for features that might predict primary tumor recurrence. The segmentation results indicated that Dice scores were similar when using multicontrast versus single T2-weighted data (0.863 vs 0.861). One week post RT, larger tumor volumes were measured, and radiomics analysis showed greater heterogeneity. In the tumor and peritumoral area, radiomics features were predictive of primary tumor recurrence (AUC: 0.79). We have created an image processing pipeline for high-throughput, reduced-bias segmentation of multiparametric tumor MRI data and radiomics analysis, to better our understanding of preclinical imaging and the insights it provides when studying new cancer therapies.
Authors
Holbrook, MD; Blocker, SJ; Mowery, YM; Badea, A; Qi, Y; Xu, ES; Kirsch, DG; Johnson, GA; Badea, CT
MLA Citation
Holbrook, M. D., et al. “MRI-Based Deep Learning Segmentation and Radiomics of Sarcoma in Mice.Tomography, vol. 6, no. 1, Mar. 2020, pp. 23–33. Pubmed, doi:10.18383/j.tom.2019.00021.
URI
https://scholars.duke.edu/individual/pub1437329
PMID
32280747
Source
pubmed
Published In
Tomography
Volume
6
Published Date
Start Page
23
End Page
33
DOI
10.18383/j.tom.2019.00021

The impact of respiratory gating on improving volume measurement of murine lung tumors in micro-CT imaging.

Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain. However, preclinical imaging faces unique challenges that emphasize the gap between mouse and man. One example is the difference in breathing patterns and breath-holding ability, which can dramatically affect tumor burden assessment in lung tissue. As part of a co-clinical trial studying immunotherapy and radiotherapy in sarcomas, we are using micro-CT of the lungs to detect and measure metastases as a metric of disease progression. To effectively utilize metastatic disease detection as a metric of progression, we have addressed the impact of respiratory gating during micro-CT acquisition on improving lung tumor detection and volume quantitation. Accuracy and precision of lung tumor measurements with and without respiratory gating were studied by performing experiments with in vivo images, simulations, and a pocket phantom. When performing test-retest studies in vivo, the variance in volume calculations was 5.9% in gated images and 15.8% in non-gated images, compared to 2.9% in post-mortem images. Sensitivity of detection was examined in images with simulated tumors, demonstrating that reliable sensitivity (true positive rate (TPR) ≥ 90%) was achievable down to 1.0 mm3 lesions with respiratory gating, but was limited to ≥ 8.0 mm3 in non-gated images. Finally, a clinically-inspired "pocket phantom" was used during in vivo mouse scanning to aid in refining and assessing the gating protocols. Application of respiratory gating techniques reduced variance of repeated volume measurements and significantly improved the accuracy of tumor volume quantitation in vivo.
Authors
Blocker, SJ; Holbrook, MD; Mowery, YM; Sullivan, DC; Badea, CT
MLA Citation
Blocker, S. J., et al. “The impact of respiratory gating on improving volume measurement of murine lung tumors in micro-CT imaging.Plos One, vol. 15, no. 2, 2020, p. e0225019. Pubmed, doi:10.1371/journal.pone.0225019.
URI
https://scholars.duke.edu/individual/pub1432965
PMID
32097413
Source
pubmed
Published In
Plos One
Volume
15
Published Date
Start Page
e0225019
DOI
10.1371/journal.pone.0225019

Photon-counting cine-cardiac CT in the mouse.

The maturation of photon-counting detector (PCD) technology promises to enhance routine CT imaging applications with high-fidelity spectral information. In this paper, we demonstrate the power of this synergy and our complementary reconstruction techniques, performing 4D, cardiac PCD-CT data acquisition and reconstruction in a mouse model of atherosclerosis, including calcified plaque. Specifically, in vivo cardiac micro-CT scans were performed in four ApoE knockout mice, following their development of calcified plaques. The scans were performed with a prototype PCD (DECTRIS, Ltd.) with 4 energy thresholds. Projections were sampled every 10 ms with a 10 ms exposure, allowing the reconstruction of 10 cardiac phases at each of 4 energies (40 total 3D volumes per mouse scan). Reconstruction was performed iteratively using the split Bregman method with constraints on spectral rank and spatio-temporal gradient sparsity. The reconstructed images represent the first in vivo, 4D PCD-CT data in a mouse model of atherosclerosis. Robust regularization during iterative reconstruction yields high-fidelity results: an 8-fold reduction in noise standard deviation for the highest energy threshold (relative to unregularized algebraic reconstruction), while absolute spectral bias measurements remain below 13 Hounsfield units across all energy thresholds and scans. Qualitatively, image domain material decomposition results show clear separation of iodinated contrast and soft tissue from calcified plaque in the in vivo data. Quantitatively, spatial, spectral, and temporal fidelity are verified through a water phantom scan and a realistic MOBY phantom simulation experiment: spatial resolution is robustly preserved by iterative reconstruction (10% MTF: 2.8-3.0 lp/mm), left-ventricle, cardiac functional metrics can be measured from iodine map segmentations with ~1% error, and small calcifications (615 μm) can be detected during slow moving phases of the cardiac cycle. Given these preliminary results, we believe that PCD technology will enhance dynamic CT imaging applications with high-fidelity spectral and material information.
Authors
Clark, DP; Holbrook, M; Lee, C-L; Badea, CT
MLA Citation
Clark, Darin P., et al. “Photon-counting cine-cardiac CT in the mouse.Plos One, vol. 14, no. 9, 2019, p. e0218417. Pubmed, doi:10.1371/journal.pone.0218417.
URI
https://scholars.duke.edu/individual/pub1411492
PMID
31536493
Source
pubmed
Published In
Plos One
Volume
14
Published Date
Start Page
e0218417
DOI
10.1371/journal.pone.0218417

Sensitization of Vascular Endothelial Cells to Ionizing Radiation Promotes the Development of Delayed Intestinal Injury in Mice.

Exposure of the gastrointestinal (GI) tract to ionizing radiation can cause acute and delayed injury. However, critical cellular targets that regulate the development of radiation-induced GI injury remain incompletely understood. Here, we investigated the role of vascular endothelial cells in controlling acute and delayed GI injury after total-abdominal irradiation (TAI). To address this, we used genetically engineered mice in which endothelial cells are sensitized to radiation due to the deletion of the tumor suppressor p53. Remarkably, we found that VE-cadherin-Cre; p53FL/FL mice, in which both alleles of p53 are deleted in endothelial cells, were not sensitized to the acute GI radiation syndrome, but these mice were highly susceptible to delayed radiation enteropathy. Histological examination indicated that VE-cadherin-Cre; p53FL/FL mice that developed delayed radiation enteropathy had severe vascular injury in the small intestine, which was manifested by hemorrhage, loss of microvessels and tissue hypoxia. In addition, using dual-energy CT imaging, we showed that VE-cadherin-Cre; p53FL/FL mice had a significant increase in vascular permeability of the small intestine in vivo 28 days after TAI. Together, these findings demonstrate that while sensitization of endothelial cells to radiation does not exacerbate the acute GI radiation syndrome, it is sufficient to promote the development of late radiation enteropathy.
Authors
Lee, C-L; Daniel, AR; Holbrook, M; Brownstein, J; Silva Campos, LD; Hasapis, S; Ma, Y; Borst, LB; Badea, CT; Kirsch, DG
MLA Citation
Lee, Chang-Lung, et al. “Sensitization of Vascular Endothelial Cells to Ionizing Radiation Promotes the Development of Delayed Intestinal Injury in Mice.Radiat Res, vol. 192, no. 3, Sept. 2019, pp. 258–66. Pubmed, doi:10.1667/RR15371.1.
URI
https://scholars.duke.edu/individual/pub1395673
PMID
31265788
Source
pubmed
Published In
Radiat Res
Volume
192
Published Date
Start Page
258
End Page
266
DOI
10.1667/RR15371.1

To gate or not to gate: An evaluation of respiratory gating techniques to improve volume measurement of murine lung tumors in micro-CT imaging

© 2019 SPIE. Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain. However, preclinical imaging is faced with unique challenges that emphasize the gap between mouse and man. One example is the difference in breathing patterns and breath-holding ability, which can dramatically affect tumor burden assessment in lung tissue. Our group is developing quantitative imaging methods for the preclinical arm of a co-clinical trial studying synergy between immunotherapy (anti-PD-1) and radiotherapy in a soft tissue sarcoma model. To mimic imaging performed in patients, primary sarcomas lesions are imaged with micro-MRI, while detection of lung metastases is performed with micro-CT. This study addresses whether respiratory gating during micro-CT acquisition improves lung tumor volume quantitation. Accuracy and precision of lung tumor measurements was determined by performing experiments involving simulations, a pocket phantom and in vivo scans with and without prospective respiratory gating. Sensitivity and precision of segmentation with and without gating was studied using simulated lung tumors. A clinically-inspired "pocket phantom" was used during in vivo mouse scanning to aid in refining and assessing the gating protocols. Finally, we performed a series of in vivo scans on tumor-bearing mice while varying the animal's position (test-retest), and performing the analyses in triplicate to assess the effects of gating. Application of respiratory gating techniques reduced variance of repeated volume measurements and significantly improved the accuracy of tumor volume quantitation in vivo.
Authors
Blocker, SJ; Holbrook, M; Mowery, YM; Badea, CT
MLA Citation
Blocker, S. J., et al. “To gate or not to gate: An evaluation of respiratory gating techniques to improve volume measurement of murine lung tumors in micro-CT imaging.” Progress in Biomedical Optics and Imaging  Proceedings of Spie, vol. 10953, 2019. Scopus, doi:10.1117/12.2512534.
URI
https://scholars.duke.edu/individual/pub1398362
Source
scopus
Published In
Progress in Biomedical Optics and Imaging Proceedings of Spie
Volume
10953
Published Date
DOI
10.1117/12.2512534

Research Areas:

Algorithms
Ambulatory Care
Amplifiers, Electronic
Analog-Digital Conversion
Angiography
Angiography, Digital Subtraction
Animals
Antigens, CD31
Artifacts
Biological Markers
Blood Vessels
Blood Volume
Bone
Brachytherapy
Calibration
Capillary Permeability
Carcinoma, Non-Small-Cell Lung
Cardiac-Gated Imaging Techniques
Cardiovascular Physiological Phenomena
Cell Line, Tumor
Child Development
Cineradiography
Colonic Neoplasms
Computer Graphics
Computer Simulation
Computers
Contrast Media
Coronary Vessels
Diagnosis, Differential
Diagnostic Imaging
Diaphragm
Disease Models, Animal
Electrocardiography
Equipment Design
Equipment Failure Analysis
Equipment Safety
Equipment and Supplies
European Union
Evaluation Studies as Topic
Feasibility Studies
Female
Fibrosarcoma
Fluorescent Antibody Technique
Fluoroscopy
Four-Dimensional Computed Tomography
Gold
Heart
Heart Ventricles
Humans
Image Enhancement
Image Interpretation, Computer-Assisted
Image Processing, Computer-Assisted
Imaging, Three-Dimensional
Infant
Iodine
Iopamidol
Least-Squares Analysis
Liposomes
Lung
Lung Compliance
Lung Diseases
Lung Neoplasms
Magnetic Resonance Imaging
Male
Mammary Neoplasms, Animal
Mammary Neoplasms, Experimental
Mammography
Metal Nanoparticles
Metals
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Mice, Transgenic
Microinjections
Microscopy
Microscopy, Fluorescence
Microvessels
Models, Biological
Models, Statistical
Models, Theoretical
Molecular Imaging
Movement
Myocardial Contraction
Myocardial Infarction
Myocardium
Nanoparticles
Neovascularization, Pathologic
Nonlinear Dynamics
Normal Distribution
Organophosphorus Compounds
Organotechnetium Compounds
Perfusion
Perfusion Imaging
Permeability
Phantoms, Imaging
Phenotype
Platelet Endothelial Cell Adhesion Molecule-1
Positive-Pressure Respiration
Product Surveillance, Postmarketing
Proto-Oncogene Proteins p21(ras)
Pulmonary Alveoli
Pulmonary Fibrosis
Quality Control
Radiation Dosage
Radiation Injuries, Experimental
Radiographic Image Enhancement
Radiographic Image Interpretation, Computer-Assisted
Radiography, Thoracic
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Regression Analysis
Reproducibility of Results
Respiration
Respiratory Mechanics
Respiratory-Gated Imaging Techniques
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Sample Size
Sarcoma
Scattering, Radiation
Sensitivity and Specificity
Sheep
Spectrometry, Fluorescence
Spectrometry, X-Ray Emission
Stochastic Processes
Stress, Physiological
Subtraction Technique
Thermodilution
Thermography
Tidal Volume
Time Factors
Tomography
Tomography Scanners, X-Ray Computed
Tomography, Emission-Computed, Single-Photon
Tomography, Optical
Tomography, X-Ray
Tomography, X-Ray Computed
Triiodobenzoic Acids
Tumor Burden
Tumor Markers, Biological
Tumor Microenvironment
Tumor Suppressor Protein p53
Tumors
Tungsten
Ventricular Function, Left
Ventricular Remodeling
Video Recording
Water
Whole Body Imaging
X-Ray Intensifying Screens
X-Ray Microtomography
X-Rays