Browsing by Author "Badea, CT"

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Open Access
Advances in micro-CT imaging of small animals.
(Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2021-08) Clark, DP; Badea, CT
Purpose
Micron-scale computed tomography (micro-CT) imaging is a ubiquitous, cost-effective, and non-invasive three-dimensional imaging modality. We review recent developments and applications of micro-CT for preclinical research.
Methods
Based on a comprehensive review of recent micro-CT literature, we summarize features of state-of-the-art hardware and ongoing challenges and promising research directions in the field.
Results
Representative features of commercially available micro-CT scanners and some new applications for both in vivo and ex vivo imaging are described. New advancements include spectral scanning using dual-energy micro-CT based on energy-integrating detectors or a new generation of photon-counting x-ray detectors (PCDs). Beyond two-material discrimination, PCDs enable quantitative differentiation of intrinsic tissues from one or more extrinsic contrast agents. When these extrinsic contrast agents are incorporated into a nanoparticle platform (e.g. liposomes), novel micro-CT imaging applications are possible such as combined therapy and diagnostic imaging in the field of cancer theranostics. Another major area of research in micro-CT is in x-ray phase contrast (XPC) imaging. XPC imaging opens CT to many new imaging applications because phase changes are more sensitive to density variations in soft tissues than standard absorption imaging. We further review the impact of deep learning on micro-CT. We feature several recent works which have successfully applied deep learning to micro-CT data, and we outline several challenges specific to micro-CT.
Conclusions
All of these advancements establish micro-CT imaging at the forefront of preclinical research, able to provide anatomical, functional, and even molecular information while serving as a testbench for translational research.
Open Access
Bridging the translational gap: Implementation of multimodal small animal imaging strategies for tumor burden assessment in a co-clinical trial
(PLOS ONE) Blocker, SJ; Mowery, YM; Holbrook, MD; Qi, Y; Kirsch, DG; Johnson, GA; Badea, CT
Open Access
Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent.
(PLoS One, 2012) Badea, CT; Athreya, KK; Espinosa, G; Clark, D; Ghafoori, AP; Li, Y; Kirsch, DG; Johnson, GA; Annapragada, A; Ghaghada, KB
PURPOSE: To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer. METHODS: Primary lung cancers with mutations in K-ras alone (Kras(LA1)) or in combination with p53 (LSL-Kras(G12D);p53(FL/FL)) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules. RESULTS: A good correlation was seen between volume and diameter-based assessment of nodules (R(2)>0.8) for both lung cancer models. The LSL-Kras(G12D);p53(FL/FL) model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in Kras(LA1) mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-Kras(G12D);p53(FL/FL) mice compared to nodules in Kras(LA1) mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules. CONCLUSIONS: The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring.
Open Access
Dual source hybrid spectral micro-CT using an energy-integrating and a photon-counting detector.
(Physics in medicine and biology, 2020-10-21) Holbrook, MD; Clark, DP; Badea, CT
Preclinical micro-CT provides a hotbed in which to develop new imaging technologies, including spectral CT using photon counting detector (PCD) technology. Spectral imaging using PCDs promises to expand x-ray CT as a functional imaging modality, capable of molecular imaging, while maintaining CT's role as a powerful anatomical imaging modality. However, the utility of PCDs suffers due to distorted spectral measurements, affecting the accuracy of material decomposition. We attempt to improve material decomposition accuracy using our novel hybrid dual-source micro-CT system which combines a PCD and an energy integrating detector. Comparisons are made between PCD-only and hybrid CT results, both reconstructed with our iterative, multi-channel algorithm based on the split Bregman method and regularized with rank-sparse kernel regression. Multi-material decomposition is performed post-reconstruction for separation of iodine (I), gold (Au), gadolinium (Gd), and calcium (Ca). System performance is evaluated first in simulations, then in micro-CT phantoms, and finally in an in vivo experiment with a genetically modified p53^fl/fl mouse cancer model with Au, Gd, and I nanoparticle (NP)-based contrasts agents. Our results show that the PCD-only and hybrid CT reconstructions offered very similar spatial resolution at 10% MTF (PCD: 3.50 lp mm^-1; hybrid: 3.47 lp mm^-1) and noise characteristics given by the noise power spectrum. For material decomposition we note successful separation of the four basis materials. We found that hybrid reconstruction reduces RMSE by an average of 37% across all material maps when compared to PCD-only of similar dose but does not provide much difference in terms of concentration accuracy. The in vivo results show separation of targeted Au and accumulated Gd NPs in the tumor from intravascular iodine NPs and bone. Hybrid spectral micro-CT can benefit nanotechnology and cancer research by providing quantitative imaging to test and optimize various NPs for diagnostic and therapeutic applications.
Open Access
Functional imaging of tumor vasculature using iodine and gadolinium-based nanoparticle contrast agents: a comparison of spectral micro-CT using energy integrating and photon counting detectors
(Physics in Medicine and Biology) Badea, CT; Clark, DP; Holbrook, M; Srivastava, M; Mowery, Y; Ghaghada, KB
Open Access
High-Resolution CT for Small-Animal Imaging Research
(Comprehensive Biomedical Physics, 2014-01-01) Badea, CT; Panetta, D
Open Access
Highly efficient detection in fluorescence tomography of quantum dots using time-gated acquisition and ultrafast pulsed laser.
(Proc SPIE Int Soc Opt Eng, 2011-01-23) Zhang, X; Badea, CT
Quantum dots (QDs) are widely used in fluorescence tomography due to its unique advantages. Despite the very high quantum efficiency of the QDs, low fluorescent signal and autofluorescence are the most fundamental limitations in optical data acquisition. These limitations are particularly detrimental to image reconstruction for animal imaging, e.g., free-space in vivo fluorescence tomography. In animals studies, fluorescent emission from exogenous fluorescent probes (e.g. QDs) cannot be effectively differentiated from endogenous broad-spectral substances (mostly proteins) using optical filters. In addition, a barrow-band fluorescent filter blocks the majority of the fluorescent light and thus makes signal acquisition very inefficient. We made use of the long fluorescent lifetime of the QDs to reject the optical signal due to the excitation light pulse, and therefore eliminated the need for a fluorescent filter during acquisition. Fluorescent emission from the QDs was excited with an ultrafast pulsed laser, and was detected using a time-gated image intensifier. A tissue-simulating imaging phantom was used to validate the proposed method. Compared to the standard acquisition method that uses a narrow-band fluorescent filter, the proposed method is significantly more efficient in data acquisition (by a factor of >10 in terms of fluorescent signal intensity) and demonstrated reduction in autofluorescence. No additional imaging artifact was observed in the tomographic reconstruction.
Open Access
Low-dose 4D cardiac imaging in small animals using dual source micro-CT.
(Phys Med Biol, 2018-01-09) Holbrook, M; Clark, DP; Badea, CT
Micro-CT is widely used in preclinical studies, generating substantial interest in extending its capabilities in functional imaging applications such as blood perfusion and cardiac function. However, imaging cardiac structure and function in mice is challenging due to their small size and rapid heart rate. To overcome these challenges, we propose and compare improvements on two strategies for cardiac gating in dual-source, preclinical micro-CT: fast prospective gating (PG) and uncorrelated retrospective gating (RG). These sampling strategies combined with a sophisticated iterative image reconstruction algorithm provide faster acquisitions and high image quality in low-dose 4D (i.e. 3D + Time) cardiac micro-CT. Fast PG is performed under continuous subject rotation which results in interleaved projection angles between cardiac phases. Thus, fast PG provides a well-sampled temporal average image for use as a prior in iterative reconstruction. Uncorrelated RG incorporates random delays during sampling to prevent correlations between heart rate and sampling rate. We have performed both simulations and animal studies to validate these new sampling protocols. Sampling times for 1000 projections using fast PG and RG were 2 and 3 min, respectively, and the total dose was 170 mGy each. Reconstructions were performed using a 4D iterative reconstruction technique based on the split Bregman method. To examine undersampling robustness, subsets of 500 and 250 projections were also used for reconstruction. Both sampling strategies in conjunction with our iterative reconstruction method are capable of resolving cardiac phases and provide high image quality. In general, for equal numbers of projections, fast PG shows fewer errors than RG and is more robust to undersampling. Our results indicate that only 1000-projection based reconstruction with fast PG satisfies a 5% error criterion in left ventricular volume estimation. These methods promise low-dose imaging with a wide range of preclinical applications in cardiac imaging.
Unknown
Micro-CT imaging of multiple K-edge elements using GaAs and CdTe photon counting detectors.
(Physics in medicine and biology, 2023-04) Allphin, AJ; Clark, DP; Thuering, T; Bhandari, P; Ghaghada, KB; Badea, CT
Objective.To evaluate the performance of two photon-counting (PC) detectors based on different detector materials, gallium arsenide (GaAs) and cadmium telluride (CdTe), for PC micro-CT imaging of phantoms with multiple contrast materials. Another objective is to determine if combining these two detectors in the same micro-CT system can offer higher spectral performance and significant artifact reduction compared to a single detector system.Approach. We have constructed a dual-detector, micro-CT system equipped with two PCDs based on different detector materials: gallium arsenide (GaAs) and cadmium telluride (CdTe). We demonstrate the performance of these detectors for PC micro-CT imaging of phantoms with up to 5 contrast materials with K-edges spread across the x-ray spectrum ranging from iodine with a K-edge at 33.2 keV to bismuth with a K-edge at 90.5 keV. We also demonstrate the use of our system to image a mouse prepared with both iodine and bismuth contrast agents to target different biological systems.Main results.When using the same dose and scan parameters, GaAs shows increased low energy (<50 keV) spectral sensitivity and specificity compared to CdTe. However, GaAs performance at high energies suffers from spectral artifacts and has comparatively low photon counts indicating wasted radiation dose. We demonstrate that combining a GaAs-based and a CdTe-based PC detector in the same micro-CT system offers higher spectral performance and significant artifact reduction compared to a single detector system.Significance.More accurate PC micro-CT using a GaAs PCD alone or in combination with a CdTe PCD could serve for developing new contrast agents such as nanoparticles that show promise in the developing field of theranostics (therapy and diagnostics).
Unknown
Micro-CT of rodents: state-of-the-art and future perspectives.
(Phys Med, 2014-09) Clark, DP; Badea, CT
Micron-scale computed tomography (micro-CT) is an essential tool for phenotyping and for elucidating diseases and their therapies. This work is focused on preclinical micro-CT imaging, reviewing relevant principles, technologies, and applications. Commonly, micro-CT provides high-resolution anatomic information, either on its own or in conjunction with lower-resolution functional imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). More recently, however, advanced applications of micro-CT produce functional information by translating clinical applications to model systems (e.g., measuring cardiac functional metrics) and by pioneering new ones (e.g. measuring tumor vascular permeability with nanoparticle contrast agents). The primary limitations of micro-CT imaging are the associated radiation dose and relatively poor soft tissue contrast. We review several image reconstruction strategies based on iterative, statistical, and gradient sparsity regularization, demonstrating that high image quality is achievable with low radiation dose given ever more powerful computational resources. We also review two contrast mechanisms under intense development. The first is spectral contrast for quantitative material discrimination in combination with passive or actively targeted nanoparticle contrast agents. The second is phase contrast which measures refraction in biological tissues for improved contrast and potentially reduced radiation dose relative to standard absorption imaging. These technological advancements promise to develop micro-CT into a commonplace, functional and even molecular imaging modality.
Unknown
MRI-Based Deep Learning Segmentation and Radiomics of Sarcoma in Mice.
(Tomography (Ann Arbor, Mich.), 2020-03) Holbrook, MD; Blocker, SJ; Mowery, YM; Badea, A; Qi, Y; Xu, ES; Kirsch, DG; Johnson, GA; Badea, CT
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.
Open Access
Small Animal X-ray Computed Tomography
(Handbook of X-ray Imaging: Physics and Technology, 2018-01-05) Badea, CT
Open Access
The impact of respiratory gating on improving volume measurement of murine lung tumors in micro-CT imaging
Blocker, SJ; Holbrook, MD; Mowery, YM; Sullivan, DC; Badea, CT
ABSTRACTSmall 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.
Open Access
The impact of respiratory gating on improving volume measurement of murine lung tumors in micro-CT imaging.
(PloS one, 2020-01) Blocker, SJ; Holbrook, MD; Mowery, YM; Sullivan, DC; Badea, CT
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.

Browsing by Author "Badea, CT"

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