Julio Cesar Cardenas Rodriguez
- Research Assistant Professor, Medical Imaging
- Research Assistant Professor, Biomedical Engineering
- Ph.D. Chemistry
- University of Arizona, Tucson, Arizona, United States
- New Models and Contrast Agents for Dynamic Contrast-Enhanced MRI
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Honors ThesisCHEM 498H (Fall 2016)
Introduction to ResearchMCB 795A (Spring 2014)
- Danford, F., Welch, E., Cárdenas-Rodríguez, J., & Strout, M. M. (2016). Analyzing parallel programming models for magnetic resonance imaging. The 29th International Workship on Languages and Compilers for Parallel Computing, 263, 184-92.
- Randtke, E. A., Pagel, M. D., & Cárdenas-Rodríguez, J. (2016). Multislice CEST MRI improves the spatial assessment of tumor pH. Journal of magnetic resonance. doi:10.1002/mrm.26348More infoPurposeMultislice maps of extracellular pH (pHe) are needed to interrogate the heterogeneities of tumors and normal organs. To address this need, we have developed a multislice chemical exchange saturation transfer (CEST) MRI acquisition method with a CEST spectrum-fitting method that measures in vivo pHe over a range of 6.3 to 7.4.MethodsThe phase offset multiplanar (POMP) method was adapted for CEST fast imaging with steady-state free precession (FISP) MRI to acquire multiple image slices with a single CEST saturation pulse. The Bloch-McConnell equations were modified to include pH based on a calibration of pH and chemical exchange rate for the contrast agent iopamidol. These equations were used to estimate the pixel-wise pHe values throughout the multislice acidoCEST MR images of the tumor, kidney, bladder, and other tissues of a MDA-MB-231 tumor model.ResultsMultislice acidoCEST MRI successfully mapped a gradient of pHe from 6.73 to 6.81 units from the tumor core to rim, and also mapped a gradient of pHe 6.56 to 6.97 across the mouse kidney. The bladder was found to be pHe 6.3.ConclusionAcidoCEST MRI with POMP acquisition and Bloch-McConnel analysis can map pHe in multiple imaging slices through the tumor, kidney, and bladder. This multislice evaluation facilitates assessments of spatial heterogeneity of tissue pHe. Magn Reson Med 000:000–000, 2016. © 2016 International Society for Magnetic Resonance in Medicine
- Randtke, E. A., Pagel, M. D., & Cárdenas-Rodríguez, J. (2016). QUESPOWR MRI: QUantification of Exchange as a function of Saturation Power On the Water Resonance. Journal of magnetic resonance, 270, 56–70.More infoQUantification of Exchange as a function of Saturation Power On the Water Resonance (QUESPOWR) MRI is a new method that can estimate chemical exchange rates. This method acquires a series of OPARACHEE MRI acquisitions with a range of RF powers for the WALTZ16∗ pulse train, which are applied on the water resonance. A QUESPOWR plot can be generated from the power dependence of the % water signal, which is similar to a QUESP plot that is generated from CEST MRI acquisition methods with RF saturation applied off-resonance from water. A QUESPOWR plot can be quantitatively analyzed using linear fitting methods to provide estimates of average chemical exchange rates. Analyses of the shapes of QUESPOWR plots can also be used to estimate relative differences in average chemical exchange rates and concentrations of biomolecules. The performance of QUESPOWR MRI was assessed via simulations, an in vitro study with iopamidol, and an in vivo study with a mouse model of mammary carcinoma. The results showed that QUESPOWR MRI is especially sensitive to chemical exchange between water and biomolecules that have intermediate to fast chemical exchange rates and chemical shifts that are close to water, which are notoriously difficult to assess with other CEST MRI methods. In addition, in vivo QUESPOWR MRI detected acidic tumor tissues relative to normal tissues that are pH-neutral, and therefore may be a new paradigm for tumor detection with MRI.
- Yoshimaru, E. S., Randtke, E. A., Pagel, M. D., & Cárdenas-Rodríguez, J. (2016). Design and optimization of pulsed Chemical Exchange Saturation Transfer MRI using a multiobjective genetic algorithm. Journal of magnetic resonance, 263, 184-92.More infoPulsed Chemical Exchange Saturation Transfer (CEST) MRI experimental parameters and RF saturation pulse shapes were optimized using a multiobjective genetic algorithm. The optimization was carried out for RF saturation duty cycles of 50% and 90%, and results were compared to continuous wave saturation and Gaussian waveform. In both simulation and phantom experiments, continuous wave saturation performed the best, followed by parameters and shapes optimized by the genetic algorithm and then followed by Gaussian waveform. We have successfully demonstrated that the genetic algorithm is able to optimize pulse CEST parameters and that the results are translatable to clinical scanners.
- Hingorani, D. V., Montano, L. A., Randtke, E. A., Lee, Y. S., Cárdenas-Rodríguez, J., & Pagel, M. D. (2015). A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals. Contrast media & molecular imaging.More infoCatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non-responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme-responsive and enzyme-unresponsive CEST signals was synthesized and characterized. The CEST signal from the aryl amide disappeared after cleavage of a dipeptidyl ligand with cathepsin B, while a salicylic acid moiety was largely unresponsive to enzyme activity. The ratiometric comparison of the two CEST signals from the same agent allowed for concentration independent measurements of enzyme activity. The chemical exchange rate of the salicylic acid moiety was unchanged after enzyme catalysis, which further validated that this moiety was enzyme-unresponsive. The temperature dependence of the chemical exchange rate of the salicylic acid moiety was non-Arrhenius, suggesting a two-step chemical exchange mechanism for salicylic acid. The good detection sensitivity at low saturation power facilitates clinical translation, along with the potentially low toxicity of a non-metallic MRI contrast agent. The modular design of the agent constitutes a platform technology that expands the variety of agents that may be employed by catalyCEST MRI for molecular imaging. Copyright © 2015 John Wiley & Sons, Ltd.
- Jones, K. M., Randtke, E. A., Howison, C. M., Cárdenas-Rodríguez, J., Sime, P. J., Kottmann, M. R., & Pagel, M. D. (2015). Measuring extracellular pH in a lung fibrosis model with acidoCEST MRI. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, 17(2), 177-84.More infoA feed-forward loop involving lactic acid production may potentially occur during the formation of idiopathic pulmonary fibrosis. To provide evidence for this feed-forward loop, we used acidoCEST MRI to measure the extracellular pH (pHe), while also measuring percent uptake of the contrast agent, lesion size, and the apparent diffusion coefficient (ADC).
- Lee, J., Cárdenas-Rodríguez, J., Pagel, M. D., Platt, S., Kent, M., & Zhao, Q. (2014). Comparison of analytical and numerical analysis of the reference region model for DCE-MRI. Magnetic resonance imaging, 32(7), 845-53.More infoThis study compared three methods for analyzing DCE-MRI data with a reference region (RR) model: a linear least-square fitting with numerical analysis (LLSQ-N), a nonlinear least-square fitting with numerical analysis (NLSQ-N), and an analytical analysis (NLSQ-A). The accuracy and precision of estimating the pharmacokinetic parameter ratios KR and VR, where KR is defined as a ratio between the two volume transfer constants, K(trans,TOI) and K(trans,RR), and VR is the ratio between the two extracellular extravascular volumes, ve,TOI and ve,RR, were assessed using simulations under various signal-to-noise ratios (SNRs) and temporal resolutions (4, 6, 30, and 60s). When no noise was added, the simulations showed that the mean percent error (MPE) for the estimated KR and VR using the LLSQ-N and NLSQ-N methods ranged from 1.2% to 31.6% with various temporal resolutions while the NLSQ-A method maintained a very high accuracy (
- Cárdenas-Rodríguez, J., Howison, C. M., & Pagel, M. D. (2013). A linear algorithm of the reference region model for DCE-MRI is robust and relaxes requirements for temporal resolution. Magnetic resonance imaging, 31(4), 497-507.More infoDynamic contrast enhanced MRI (DCE-MRI) has utility for improving clinical diagnoses of solid tumors, and for evaluating the early responses of anti-angiogenic chemotherapies. The Reference Region Model (RRM) can improve the clinical implementation of DCE-MRI by substituting the contrast enhancement of muscle for the Arterial Input Function that is used in traditional DCE-MRI methodologies. The RRM is typically fitted to experimental results with a non-linear least squares algorithm. This report demonstrates that this algorithm produces inaccurate and imprecise results when DCE-MRI results have low SNR or slow temporal resolution. To overcome this limitation, a linear least-squares algorithm has been derived for the Reference Region Model. This new algorithm improves accuracy and precision of fitting the Reference Region Model to DCE-MRI results, especially for voxel-wise analyses. This linear algorithm is insensitive to injection speeds, and has 300- to 8000-fold faster calculation speed relative to the non-linear algorithm. The linear algorithm produces more accurate results for over a wider range of permeabilities and blood volumes of tumor vasculature. This new algorithm, termed the Linear Reference Region Model, has strong potential to improve clinical DCE-MRI evaluations.
- Cárdenas-Rodríguez, J., Howison, C. M., Matsunaga, T. O., & Pagel, M. D. (2013). A reference agent model for DCE MRI can be used to quantify the relative vascular permeability of two MRI contrast agents. Magnetic resonance imaging, 31(6), 900-10.More infoDynamic Contrast Enhancement (DCE) MRI has been used to measure the kinetic transport constant, K(trans), which is used to assess tumor angiogenesis and the effects of anti-angiogenic therapies. Standard DCE MRI methods must measure the pharmacokinetics of a contrast agent in the blood stream, known as the Arterial Input Function (AIF), which is then used as a reference for the pharmacokinetics of the agent in tumor tissue. However, the AIF is difficult to measure in pre-clinical tumor models and in patients. Moreover the AIF is dependent on the Fahraeus effect that causes a highly variable hematocrit (Hct) in tumor microvasculature, leading to erroneous estimates of K(trans). To overcome these problems, we have developed the Reference Agent Model (RAM) for DCE MRI analyses, which determines the relative K(trans) of two contrast agents that are simultaneously co-injected and detected in the same tissue during a single DCE-MRI session. The RAM obviates the need to monitor the AIF because one contrast agent effectively serves as an internal reference in the tumor tissue for the other agent, and it also eliminates the systematic errors in the estimated K(trans) caused by assuming an erroneous Hct. Simulations demonstrated that the RAM can accurately and precisely estimate the relative K(trans) (R(Ktrans)) of two agents. To experimentally evaluate the utility of RAM for analyzing DCE MRI results, we optimized a previously reported multiecho (19)F MRI method to detect two perfluorinated contrast agents that were co-injected during a single in vivo study and selectively detected in the same tumor location. The results demonstrated that RAM determined R(Ktrans) with excellent accuracy and precision.
- Cárdenas-Rodríguez, J., Li, Y., Galons, J., Cornnell, H., Gillies, R. J., Pagel, M. D., & Baker, A. F. (2012). Imaging biomarkers to monitor response to the hypoxia-activated prodrug TH-302 in the MiaPaCa2 flank xenograft model. Magnetic resonance imaging, 30(7), 1002-9.More infoTH-302, a hypoxia-activated anticancer prodrug, was evaluated for antitumor activity and changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in a mouse model of pancreatic cancer. TH-302 monotherapy resulted in a significant delay in tumor growth compared to vehicle-treated controls. TH-302 treatment was also associated with a significant decrease in the volume transfer constant (K(trans)) compared to vehicle-treated controls 1 day following the first dose measured using DCE-MRI. This early decrease in K(trans) following the first dose as measured is consistent with selective killing of the hypoxic fraction of cells which are associated with enhanced expression of hypoxia inducible transcription factor-1 alpha that regulates expression of permeability and perfusion factors including vascular endothelial growth factor-A. No changes were observed in DW-MRI following treatment with TH-302, which may indicate that this technique is not sensitive enough to detect changes in small hypoxic fractions of the tumor targeted by TH-302. These results suggest that changes in tumor permeability and/or perfusion may be an early imaging biomarker for response to TH-302 therapy.
- Notario, R., Roux, M. V., Cuevas, G., Cardenas, J., Leyva, V., & Juaristi, E. (2006). Computational study of 1,3-dithiane 1,1-dioxide (1,3-dithiane sulfone). Description of the inversion process and manifestation of stereoelectronic effects on (1)J(C-H) coupling constants. JOURNAL OF PHYSICAL CHEMISTRY A, 110(24), 7703-7712.
- Garcia-Jimenez, F., Zuniga, O., Garcia, Y., Cardenas, J., & Cuevas, G. (2005). Experimental and theoretical study of the products from the spontaneous dimerization of DL- and D-glyceraldehyde. JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY, 16(3A), 467-476.
- DegrandChamp, J. B., Whisenant, J. G., Arlinghaus, L. R., Yankeelov, T. E., & Cárdenas-Rodríguez, J. (2016, March). Predicting response before initiation of neoadjuvant chemotherapy in breast cancer using new methods for the analysis of dynamic contrast enhanced MRI (DCE MRI) data. SPIE Medical Imaging 2016. San Diego, California.
- Cardenas Rodriguez, J., & Pagel, M. D. (2015, May). A robust method to estimate CEST MRI parametric maps in vivo: Simultaneous quantification of concentration and exchange rate by minimizing the Lp norm. ISMRM 23rd Annual Meeting and Exhibition 2015. Toronto, Canada: International Society for Magnetic Resonance in Medicine.
- Huppe, C., Morscher, S., Burton, N. C., Pagel, M., & Cardenas Rodriguez, J. (2015, September). Quantitative pharmacokinetic analysis of dynamic contrast-enhanced multispectral optoacoustic tomography (DCE-MSOT). WMIC. Honolulu, Hawaii: World Molecular Imaging Society.
- Montano, L. A., Pagel, M. D., & Cárdenas-Rodríguez, J. (2015, May). Quantum Chemical Prediction and Experimental Validation of the Characteristics of diaCEST MRI Contrast Agents. ISMRM 23rd Annual Meeting and Exhibition 2015. Toronto, Canada: International Society for Magnetic Resonance in Medicine.
- Randtke, E. A., Pagel, M. D., & Cardenas Rodriguez, J. (2015, May). Improved diagnosis of tumor tissues with QUESPOWR MRI. ISMRM 23rd Annual Meeting and Exhibition 2015. Toronto, Canada: International Society for Magnetic Resonance in Medicine.
- Randtke, E. A., Pagel, M. D., & Cardenas Rodriguez, J. (2015, May). Optimization of Simultaneous Multislice Acquisition for AcidoCEST MRI. ISMRM 23rd Annual Meeting and Exhibition 2015. Toronto, Canada: International Society for Magnetic Resonance in Medicine.
- Yoshimaru, E., Randtke, E. A., Pagel, M. D., & Cardenas Rodriguez, J. (2015, May). Optimization of pulsed CEST imaging using genetic algorithm. ISMRM 23rd Annual Meeting and Exhibition 2015. Toronto, Canada: International Society for Magnetic Resonance in Medicine.
- Degrandchamp, J., & Cárdenas-Rodríguez, J. (2015, October). fitdcemri: a Matlab function for the analysis of DCE MRI data. Open Science Framework. http://doi.org/10.17605/OSF.IO/H3N48