Jean-Philippe Galons
- Associate Research Professor
- Associate, Center for Toxicology
- (520) 626-8719
- Radiology Medical Research Lab, Rm. 126
- Tucson, AZ 85721
- jgalons@arizona.edu
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Journals/Publications
- Altbach, M. I., Bilgin, A., Martin, D. R., Umapathy, L., Johnson, K., Galons, J., & Keerthivasan, M. B. (2021). Abdominal T2-weighted Imaging and T2 Mapping using a Variable Flip Angle Radial Turbo Spin Echo Technique. Journal of Magnetic Resonance Imaging.
- Berry, D. B., Galinsky, V. L., Hutchinson, E. B., Galons, J. P., Ward, S. R., & Frank, L. R. (2023). Double pulsed field gradient diffusion MRI to assess skeletal muscle microstructure. Magnetic resonance in medicine, 90(4), 1582-1593.More infoPreliminary study to determine whether double pulsed field gradient (PFG) diffusion MRI is sensitive to key features of muscle microstructure related to function.
- Galons, J., Dettman, D. L., Wondrak, G. T., & Jandova, J. (2023).
Systemic deuteration of SCID mice using the water‐isotopologue deuterium oxide (D 2 O) inhibits tumor growth in an orthotopic bioluminescent model of human pancreatic ductal adenocarcinoma
. Molecular Carcinogenesis. doi:10.1002/mc.23509More infoSince its initial discovery as a natural isotopologue of dihydrogen oxide (1 H2 O), extensive research has focused on the biophysical, biochemical, and pharmacological effects of deuterated water (2 H2 O [D2 O, also referred to as "heavy water"]). Using a panel of cultured human pancreatic ductal adenocarcinoma (PDAC) cells we have profiled (i) D2 O-induced phenotypic antiproliferative and apoptogenic effects, (ii) redox- and proteotoxicity-directed stress response gene expression, and (iii) phosphoprotein-signaling related to endoplasmic reticulum (ER) and MAP-kinase stress response pathways. Differential array analysis revealed early modulation of stress response gene expression in both BxPC-3 and PANC-1 PDAC cells elicited by D2 O (90%; ≤6 h; upregulated: HMOX1, NOS2, CYP2E1, CRYAB, DDIT3, NFKBIA, PTGS1, SOD2, PTGS2; downregulated: RUNX1, MYC, HSPA8, HSPA1A) confirmed by independent RT-qPCR analysis. Immunoblot-analysis revealed rapid (≤6 h) onset of D2 O-induced MAP-kinase signaling (p-JNK, p-p38) together with ER stress response upregulation (p-eIF2α, ATF4, XBP1s, DDIT3/CHOP). Next, we tested the chemotherapeutic efficacy of D2 O-based drinking water supplementation in an orthotopic PDAC model employing firefly luciferase-expressing BxPC-3-FLuc cells in SCID mice. First, feasibility and time course of systemic deuteration (30% D2 O in drinking water; 21 days) were established using time-resolved whole-body proton magnetic resonance imaging and isotope-ratio mass spectrometry-based plasma (D/H)-analysis. D2 O-supplementation suppressed tumor growth by almost 80% with downregulated expression of PCNA, MYC, RUNX1, and HSP70 while increasing tumor levels of DDIT3/CHOP, HO-1, and p-eIF2α. Taken together, these data demonstrate for the first time that pharmacological induction of systemic deuteration significantly reduces orthotopic tumor burden in a murine PDAC xenograft model. - Zapata Bustos, R., Coletta, D. K., Galons, J. P., Davidson, L. B., Langlais, P. R., Funk, J. L., Willis, W. T., & Mandarino, L. J. (2023). Nonequilibrium thermodynamics and mitochondrial protein content predict insulin sensitivity and fuel selection during exercise in human skeletal muscle. Frontiers in physiology, 14, 1208186.More infoMany investigators have attempted to define the molecular nature of changes responsible for insulin resistance in muscle, but a molecular approach may not consider the overall physiological context of muscle. Because the energetic state of ATP (ΔG) could affect the rate of insulin-stimulated, energy-consuming processes, the present study was undertaken to determine whether the thermodynamic state of skeletal muscle can partially explain insulin sensitivity and fuel selection independently of molecular changes. P-MRS was used with glucose clamps, exercise studies, muscle biopsies and proteomics to measure insulin sensitivity, thermodynamic variables, mitochondrial protein content, and aerobic capacity in 16 volunteers. After showing calibrated P-MRS measurements conformed to a linear electrical circuit model of muscle nonequilibrium thermodynamics, we used these measurements in multiple stepwise regression against rates of insulin-stimulated glucose disposal and fuel oxidation. Multiple linear regression analyses showed 53% of the variance in insulin sensitivity was explained by 1) VO ( = 0.001) and the 2) slope of the relationship of ΔG with the rate of oxidative phosphorylation ( = 0.007). This slope represents conductance in the linear model (functional content of mitochondria). Mitochondrial protein content from proteomics was an independent predictor of fractional fat oxidation during mild exercise (R = 0.55, = 0.001). Higher mitochondrial functional content is related to the ability of skeletal muscle to maintain a greater ΔG, which may lead to faster rates of insulin-stimulated processes. Mitochondrial protein content can explain fractional fat oxidation during mild exercise.
- Altbach, M. I., Martin, D. R., Galons, J., Johnson, K., Bilgin, A., Keerthivasan, M. B., Fu, Z., & Li, Z. (2021). Rapid high-resolution volumetric T1 mapping using a highly accelerated Inversion-Recovery Radial FLASH technique. Magnetic Resonance Imaging, 79, 28-37.
- Tapia, E., Villa-Guillen, D. E., Chalasani, P., Centuori, S., Roe, D. J., Guillen-Rodriguez, J., Huang, C., Galons, J. P., Thomson, C. A., Altbach, M., Trujillo, J., Pinto, L., Martinez, J. A., Algotar, A. M., & Chow, H. S. (2021). A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density. Breast cancer research and treatment, 190(1), 69-78.More infoObesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk.
- Galons, J. P. (2020). Editorial for "Relative Enhanced Diffusivity in Prostate Cancer: Protocol Optimization and Diagnostic Potential". Journal of magnetic resonance imaging : JMRI, 51(6), 1911.
- Galons, J., Trouard, T. P., Arias Lorza, A., Ravi, H., Parra, N., Von Hoff, D., Read, W., Tibes, R., Korn, R., & Raghunand, N. (2020). Dose–response assessment by quantitative MRI in a phase 1 clinical study of the anti-cancer vascular disrupting agent crolibulin. Scientific Reports, 10(1), 14449. doi:10.1038/s41598-020-71246-w
- Witte, M. H., Galons, J., Saranathan, M., Kalb, B. T., Mustacich, D., Moedano, L., & Seckeler, M. (2020). Non contrast MR lymphography of rare lymphatic abnormalities. Lymphology, 53(3), 133-137.
- Blew, R. M., Lee, V. R., Bea, J. W., Hetherington-Rauth, M. C., Galons, J. P., Altbach, M. I., Lohman, T. G., & Going, S. B. (2019). Validation of Peripheral Quantitative Computed Tomography-Derived Thigh Adipose Tissue Subcompartments in Young Girls Using a 3 T MRI Scanner. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry, 21(4), 583-594.More infoThe ability to assess skeletal muscle adipose tissue is important given the negative clinical implications associated with greater fat infiltration of the muscle. Computed tomography and magnetic resonance imaging (MRI) are highly accurate for measuring appendicular soft tissue and muscle composition, but have limitations. Peripheral quantitative computed tomography (pQCT) is an alternative that investigators find valuable because of its low radiation, fast scan time, and comparatively lower costs. The present investigation sought to assess the accuracy of pQCT-derived estimates of total, subcutaneous, skeletal muscle, intermuscular, and calculated intramuscular adipose tissue areas, and muscle density in the midthigh of young girls using the gold standard, 3 T MRI, as the criterion. Cross-sectional data were analyzed for 26 healthy girls aged 9-12 years. Midthigh soft tissue composition was assessed by both pQCT and 3 T MRI. Mean tissue area for corresponding adipose compartments by pQCT and MRI was compared using t tests, regression analysis, and Bland-Altman plots. Muscle density was regressed on MRI skeletal muscle adipose tissue, intermuscular adipose tissue, and intramuscular adipose tissue, each expressed as a percentage of total muscle area. Correlations were high between MRI and pQCT for total adipose tissue (r = 0.98), subcutaneous adipose tissue (r = 0.95), skeletal muscle adipose tissue (r = 0.83), and intermuscular adipose tissue (r = 0.82), and pQCT muscle density correlated well with both MRI skeletal muscle adipose tissue (r = 0.70) and MRI intermuscular adipose tissue (r = 0.70). There was a slight, but statistically significant underestimation by pQCT for total and subcutaneous adipose tissue, whereas no significant difference was observed for skeletal muscle adipose tissue. Both pQCT-estimated intramuscular adipose tissue and muscle density were weakly correlated with MRI-intramuscular adipose tissue. We conclude that pQCT is a valid measurement technique for estimating all adipose subcompartments, except for intramuscular adipose tissue, for the midthigh region in young/adolescent girls.
- Li, Z., Bilgin, A., Johnson, K., Galons, J. P., Vedantham, S., Martin, D. R., & Altbach, M. I. (2019). Rapid high-resolution T mapping using a highly accelerated radial steady-state free-precession technique. Journal of magnetic resonance imaging : JMRI, 49(1), 239-252.More infoT mapping is often used in some clinical protocols. Existing techniques are limited in slice coverage, and/or spatial-temporal resolution, or require long acquisitions. Here we present a multi-slice inversion-recovery (IR) radial steady-state free precession (radSSFP) pulse sequence combined with a principal component (PC) based reconstruction that overcomes these limitations.
- Blew, R., Lee, V., Bea, J. W., Hetherington-Rauth, M., Galons, J., Altbach, M. I., Lohman, T. G., & Going, S. B. (2018). Validation of Peripheral Quantitative Computed Tomography-Derived Thigh Adipose Tissue Subcompartments in Young Girls Using a 3 T MRI Scanner. Journal of Clinical Densitometry, 583-594.
- Ding, J., Stopeck, A. T., Gao, Y., Marron, M. T., Wertheim, B. C., Altbach, M. I., Galons, J. P., Roe, D. J., Wang, F., Maskarinec, G., Thomson, C. A., Thompson, P. A., & Huang, C. (2018). Reproducible automated breast density measure with no ionizing radiation using fat-water decomposition MRI. Journal of magnetic resonance imaging : JMRI, 48(4), 971-981.More infoIncreased breast density is a significant independent risk factor for breast cancer, and recent studies show that this risk is modifiable. Hence, breast density measures sensitive to small changes are desired.
- Galons, J., Ding, J., Stopeck, A. T., Gao, Y., Marron, M. T., Wertheim, B. C., Altbach, M. I., Roe, D. J., Wang, F., Maskarinec, G., Thomson, C. A., Thompson, P. A., & Huang, C. (2018). Reproducible automated breast density measure with no ionizing radiation using fat-water decomposition MRI. Journal of Magnetic Resonance Imaging, 48(4), 971-981. doi:10.1002/jmri.26041
- Lee, V., Blew, R., Hetherington-Rauth, M., Blew, D., Galons, J. P., Hagio, T., Bea, J., Lohman, T., & Going, S. (2018). Estimation of visceral fat in 9- to 13-year-old girls using dual-energy X-ray absorptiometry (DXA) and anthropometry. Obesity science & practice, 4(5), 437-447.More infoAccumulation of visceral fat (VF) in children increases the risk of cardiovascular disease and type 2 diabetes, and measurement of VF in children using computed tomography and magnetic resonance imaging (MRI) is expensive. Dual-energy X-ray absorptiometry (DXA) may provide a low-cost alternative. This study aims to determine if DXA VF estimates can accurately estimate VF in young girls, determine if adding anthropometry would improve the estimate and determine if other DXA fat measures, with and without anthropometry, could be used to estimate VF in young girls.
- Galons, J. (2017).
Diffusion weighted and diffusion tensor imaging: A clinical guide
. Journal of Magnetic Resonance Imaging, 46(4), 1230-1231. doi:10.1002/jmri.25621 - Galons, J. P. (2017). Diffusion weighted and diffusion tensor imaging: A clinical guide. Journal of magnetic resonance imaging : JMRI.
- Galons, J. P., Harland, R. C., Taylor, M. J., Steyn, L. V., Papas, K. K., Pandey, A., Min, C. G., & Harland, R. C. (2017).
Quality Assessments of Persufflation and Cold Storage Preservation in Subnormothermic Isolated Porcine Kidneys
. Transplantation, 101, S85. doi:10.1097/01.tp.0000525113.95879.8e - Galons, J., Stopeck, A., Marron, M. T., Wertheim, B. C., Wang, F., Thomson, C. A., Thompson, P. A., Stopeck, A., Roe, D. J., Maskarinec, G., Huang, C., Gao, Y., Ding, J., & Altbach, M. I. (2017).
Abstract P3-02-03: Accurate and reliable automated breast density measurements with no ionizing radiation using fat-water decomposition MRI
. Cancer Research, 77(4_Supplement), P3-02-03-P3-02-03. doi:10.1158/1538-7445.sabcs16-p3-02-03More infoObjective Breast density(BD) is a measure of the distribution of variable tissue types within the breast and higher BD has been shown to positively correlate with breast cancer risk. As such, the accurate measurement of BD has become a priority for risk assessment and for evaluating the effects of prevention strategies aimed at reducing BD. Mammography(MG) is the most common method of BD determination but is limited by the exposure to ionizing radiation, particularly for studies requiring repeated measures. BD derived from fat-water decomposition magnetic resonance imaging(FWMRI-BD) has been proposed as an alternative, safe, and quantitative method for BD. To optimize its use, we developed a new FWMRI-BD that is automated, more accurate and reliable. In this study, we compare our automated method to digital MG and a previous reported algorithm for MRI derived BD. Methods From a completed prevention trial, 42 pre- and post-menopausal patients receiving tamoxifen therapy for early stage breast cancer or as primary chemoprevention were identified. Patients had undergone prior digital MG within 6 months from the date of MRI scan and MG-BD was calculated using a well-established method(Cumulus). MRI scans were performed on a 1.5T GE Signa NV-CV/i scanner using an axial radial IDEAL-GRASE sequence to generate quantitative fat fraction maps of the entire breast. Total acquisition time was Results Table 1 shows the correlation and reliability analysis results between MG-BD and FWMRI-BD. Both FWMRI-BD measures(Fra80 and FraG+W) were strongly correlated with MG-BD. More importantly, they exhibit superior test-retest reliability(ICC>0.98) compared to MG-BD values from the literature(reported ICC range 0.91-0.95). FraG+W showed improvement over Fra80 in all measures tested including correlation to MG-BD, dynamic range, standard errors and ICC. Conclusion The refined and automated FWMRI-BD that quantifies the entire fibroglandular and water content of the breast(FraG+W) strongly correlates with MG-BD and is more accurate and reliable than previous FWMRI-BD method. Acknowledgement NIH grants CA149417, CA161534. Citation Format: Ding J, Thompson PA, Gao Y, Marron MT, Wertheim BC, Altbach MI, Galons J-P, Roe DJ, Wang F, Maskarinec G, Thomson CA, Stopeck A, Huang C. Accurate and reliable automated breast density measurements with no ionizing radiation using fat-water decomposition MRI [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-02-03. - Pandey, A., Yoruk, U., Keerthivasan, M., Galons, J. P., Sharma, P., Johnson, K., Martin, D. R., Altbach, M. I., Bilgin, A., & Saranathan, M. (2017). Multiresolution imaging using golden angle stack-of-stars and compressed sensing for dynamic MR urography. Journal of magnetic resonance imaging : JMRI, 46(1), 303-311.More infoTo develop a novel multiresolution MRI methodology for accurate estimation of glomerular filtration rate (GFR) in vivo.
- Thomson, C. A., Chow, H., Wertheim, B. C., Roe, D. J., Stopeck, A., Maskarinec, G., Altbach, M., Chalasani, P., Huang, C., Strom, M. B., Galons, J. P., & Thompson, P. A. (2017). A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast cancer research and treatment, 165(1), 97-107.
- Brand, J. F., Furenlid, L. R., Altbach, M. I., Galons, J., Bhattacharyya, A., Sharma, P., Bhattacharyya, T., Bilgin, A., & Martin, D. R. (2016). Task-based optimization of flip angle for fibrosis detection in T1-weighted MRI of liver. Journal of medical imaging (Bellingham, Wash.), 3(3), 035502.More infoChronic liver disease is a worldwide health problem, and hepatic fibrosis (HF) is one of the hallmarks of the disease. The current reference standard for diagnosing HF is biopsy followed by pathologist examination; however, this is limited by sampling error and carries a risk of complications. Pathology diagnosis of HF is based on textural change in the liver as a lobular collagen network that develops within portal triads. The scale of collagen lobules is characteristically in the order of 1 to 5 mm, which approximates the resolution limit of in vivo gadolinium-enhanced magnetic resonance imaging in the delayed phase. We use MRI of formalin-fixed human ex vivo liver samples as phantoms that mimic the textural contrast of in vivo Gd-MRI. We have developed a local texture analysis that is applied to phantom images, and the results are used to train model observers to detect HF. The performance of the observer is assessed with the area-under-the-receiver-operator-characteristic curve (AUROC) as the figure-of-merit. To optimize the MRI pulse sequence, phantoms were scanned with multiple times at a range of flip angles. The flip angle that was associated with the highest AUROC was chosen as optimal for the task of detecting HF.
- Martinez, J. A., Chalasani, P., Thomson, C. A., Roe, D., Altbach, M., Galons, J., Stopeck, A., Thompson, P. A., Villa-Guillen, D. E., & Chow, H. S. (2016). Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. BMC cancer, 16, 500.More infoTwo-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk.
- Huang, C., Galons, J., Graff, C. G., Clarkson, E. W., Bilgin, A., Kalb, B., Martin, D. R., & Altbach, M. I. (2015). Correcting partial volume effects in biexponential T2 estimation of small lesions. Magnetic resonance in medicine, 73(4), 1632-42.More infoT2 mapping provides a quantitative approach for focal liver lesion characterization. For small lesions, a biexponential model should be used to account for partial volume effects (PVE). However, conventional biexponential fitting suffers from large uncertainty of the fitted parameters when noise is present. The purpose of this work is to develop a more robust method to correct for PVE affecting small lesions.
- Rosado-Toro, J. A., Barr, T., Galons, J., Marron, M. T., Stopeck, A., Thomson, C., Thompson, P., Carroll, D., Wolf, E., Altbach, M. I., & Rodríguez, J. J. (2015). Automated breast segmentation of fat and water MR images using dynamic programming. Academic radiology, 22(2), 139-48.More infoTo develop and test an algorithm that outlines the breast boundaries using information from fat and water magnetic resonance images.
- Stephen, R. M., Jha, A. K., Roe, D. J., Trouard, T. P., Galons, J., Kupinski, M. A., Frey, G., Cui, H., Squire, S., Pagel, M. D., Rodriguez, J. J., Gillies, R. J., & Stopeck, A. T. (2015). Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis. Magnetic Resonance Imaging, 33(10), 1267-73.
- Stephen, R. M., Jha, A. K., Roe, D. J., Trouard, T. P., Galons, J., Kupinski, M. A., Frey, G., Cui, H., Squire, S., Pagel, M. D., Rodriguez, J. J., Gillies, R. J., & Stopeck, A. T. (2015). Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis. Magnetic resonance imaging, 33(10), 1267-73.More infoTo assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis.
- Altbach, M. I., Clarkson, E. W., Galons, J., Huang, C., Graff, C. G., Bilgin, A., Kalb, B., & Martin, D. R. (2014). Correcting partial volume effects in biexponential T 2 estimation of small lesions. Magnetic Resonance in Medicine, 73(4), 1632-1642. doi:10.1002/mrm.25250
- Sharma, P., Martin, D. R., Galons, J. P., Sharma, P., Martin, D. R., Kalb, B., & Altbach, M. I. (2014).
Measurement of liver fat fraction and iron with MRI and MR spectroscopy techniques.
. Diagnostic and interventional radiology (Ankara, Turkey), 20(1), 17-26. doi:10.5152/dir.2013.13124More infoDiffuse liver disease is a widespread global healthcare burden, and the abnormal accumulation of lipid and/or iron is common to important disease processes. Developing the improved methods for detecting and quantifying liver lipid and iron is an important clinical need. The inherent risk, invasiveness, and sampling error of liver biopsy have prompted the development of noninvasive imaging methods for lipid and iron assessment. Ultrasonography and computed tomography have the ability to detect diffuse liver disease, but with limited accuracy. The purpose of this review is to describe the current state-of-the-art methods for quantifying liver lipid and iron using magnetic resonance imaging and spectroscopy, including their implementation, benefits, and potential pitfalls. Imaging- and spectroscopy-based methods are naturally suited for lipid and iron quantification. Lipid can be detected and decomposed from the inherent chemical shift between lipid and water signals, whereas iron imparts significant paramagnetic susceptibility to tissue, which accelerates proton relaxation. However, measurements of these biomarkers are confounded by technical and biological effects. Current methods must address these factors to allow a precise correlation between the lipid fraction and iron concentration. Although this correlation becomes increasingly challenging in the presence of combined lipid and iron accumulation, advanced techniques show promise for delineating these quantities through multi-lipid peak analysis, T2 water mapping, and fast single-voxel water-lipid spectroscopy. - Ainapurapu, B., Galons, J. P., Squire, S., Singh, J., Kc, D. B., Huang, C., Barr, T., Altbach, M. I., Ainapurapu, B., & Abidov, A. (2012).
T2 mapping of the heart with high temporal and spatial resolution using a radial double inversion fast spin-echo pulse sequence with view sharing
. Journal of Cardiovascular Magnetic Resonance, 14(1), 1-2. doi:10.1186/1532-429x-14-s1-o112More infoSummary A double inversion radial fast spin echo (DIR-RADFSE) has been developed to obtain T2 maps of the heart with high-temporal and spatial resolution from data acquired in as ingle breath hold. The method allows for the quantitative assessment of inflammation in the heart. Background While DE imaging is considered a gold standard in the evaluation of myocardial scar/viability in patients with old MI or cardiomyopathy, a few recent publications demonstrate a higher diagnostic sensitivity of T2weighted techniques in patients with Non-STEMI and myocarditis where changes in T2-weighting are due to inflammation in the myocardium leading to edema (Abdel-Aty H, JACC 53:1194, 2009; Tilak GS, Invest - Cardenas-rodriguez, J., Baker, A. F., Galons, J. P., Pagel, M. D., Li, Y., Gillies, R. J., Cornnell, H. H., & 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. doi:10.1016/j.mri.2012.02.015More 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. - Secomb, T. W., Galons, J. P., Trouard, T. P., Secomb, T. W., Russell, G., & Harkins, K. D. (2012).
A finite difference method with periodic boundary conditions for simulations of diffusion-weighted magnetic resonance experiments in tissue.
. Physics in medicine and biology, 57(4), N35-46. doi:10.1088/0031-9155/57/4/n35More infoA new finite difference (FD) method for calculating the time evolution of complex transverse magnetization in diffusion-weighted magnetic resonance imaging and spectroscopy experiments is described that incorporates periodic boundary conditions. The new FD method relaxes restrictions on the allowable time step size employed in modeling which can significantly reduce computation time for simulations of large physical extent and allow for more complex, physiologically relevant, geometries to be simulated. - Galons, J. P., Trouard, T. P., Harkins, K. D., & Divijak, J. L. (2011).
Changes in intracellular water diffusion and energetic metabolism in response to ischemia in perfused C6 rat glioma cells.
. Magnetic resonance in medicine, 66(3), 859-67. doi:10.1002/mrm.22866More infoThis work reports results of experiments in hollow-fiber bioreactor C6 glioma cell cultures where the apparent diffusion coefficient (ADC) of intracellular water (iADC) was measured at diffusion times between 0.83 and 40 ms. The experiments were carried out before and after the onset of permanent ischemia. The changes in iADC following ischemia were dependent on the diffusion time employed in the experiment. An ischemia-induced decrease in the iADC was measured at short diffusion times, while at long diffusion times the iADC increased. Decreases in the iADC measured at short diffusion times are interpreted to be a result of a decrease in the intrinsic diffusivity of intracellular water due to energy failure. Increases in iADC measured at long diffusion times, are interpreted to result from cell swelling. - Secomb, T. W., Galons, J. P., Trouard, T. P., Secomb, T. W., & Harkins, K. D. (2009).
Assessment of the effects of cellular tissue properties on ADC measurements by numerical simulation of water diffusion.
. Magnetic resonance in medicine, 62(6), 1414-22. doi:10.1002/mrm.22155More infoThe apparent diffusion coefficient (ADC), as measured by diffusion-weighted MRI, has proven useful in the diagnosis and evaluation of ischemic stroke. The ADC of tissue water is reduced by 30-50% following ischemia and provides excellent contrast between normal and affected tissue. Despite its clinical utility, there is no consensus on the biophysical mechanism underlying the reduction in ADC. In this work, a numerical simulation of water diffusion is used to predict the effects of cellular tissue properties on experimentally measured ADC. The model indicates that the biophysical mechanisms responsible for changes in ADC postischemia depend upon the time over which diffusion is measured. At short diffusion times, the ADC is dependent upon the intrinsic intracellular diffusivity, while at longer, clinically relevant diffusion times, the ADC is highly dependent upon the cell volume fraction. The model also predicts that at clinically relevant diffusion times, the 30-50% drop in ADC after ischemia can be accounted for by cell swelling alone when intracellular T(2) is allowed to be shorter than extracellular T(2). - Galons, J. P., Trouard, T. P., Harkins, K. D., Gillies, R. J., & Divijak, J. L. (2008).
Ischemia-induced changes of intracellular water diffusion in rat glioma cell cultures.
. Magnetic resonance in medicine, 60(2), 258-64. doi:10.1002/mrm.21616More infoDiffusion-weighted MRI is commonly used in the diagnosis and evaluation of ischemic stroke because of the rapid decrease observed in the apparent diffusion coefficient (ADC) of tissue water following ischemia. Although this observation has been clinically useful for many years, the biophysical mechanisms underlying the reduction of tissue ADC are still unknown. To help elucidate these mechanisms, we have employed a novel three-dimensional (3D) hollow-fiber bioreactor (HFBR) perfused cell culture system that enables cells to be grown to high density and studied via MRI and MRS. By infusing contrast media into the HFBR, signals from intracellular water and extracellular water are spectroscopically resolved and can be investigated individually. Diffusion measurements carried out on C6 glioma HFBR cell cultures indicate that ischemia-induced cellular swelling results in an increase in the ADC of intracellular water from 0.35 microm(2)/ms to approximately 0.5 microm(2)/ms (diffusion time = 25 ms). - Galons, J. P., Trouard, T. P., Lope-piedrafita, S., Gillies, R. J., & Garcia-martin, M. L. (2008).
Longitudinal diffusion tensor imaging in a rat brain glioma model.
. NMR in biomedicine, 21(8), 799-808. doi:10.1002/nbm.1256More infoIn order to investigate the properties of water motion within and around brain tumors as a function of tumor growth, longitudinal diffusion tensor imaging (DTI) was carried out in a rat brain glioma (C6) model. As tumors grew in size, significant anisotropy of water diffusion was seen both within and around the tumor. The tissue water surrounding the tumor exhibited high planar anisotropy, as opposed to the linear anisotropy normally seen in white matter, indicating that cells were experiencing stress in a direction normal to the tumor border. When tumors were sufficiently large, significant anisotropy was also seen within the tumor because of longer-range organization of cancer cells within the tumor borders. These findings have important implications for diffusion-weighted MRI experiments examining tumor growth and response to therapy. - Jordan, B. F., Gillies, R. J., & Galons, J. P. (2007). Post treatment changes in tumor microenvironment: dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Cancer ImagingLung and Breast Carcinomas, 235-248. doi:10.1016/b978-012374212-4.50094-8More infoPublisher Summary One method for noninvasively assessing tumor physiology and metabolism is magnetic resonance imaging (MRI). This chapter presents the potential of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) to monitor post-treatment changes in the tumor microenvironment in both the preclinical and clinical settings. DCE-MRI is widely used in the diagnosis and staging of cancer and is emerging as a promising method for monitoring tumor response to treatment. It is used experimentally to monitor the effectiveness of a variety of treatments, including chemotherapy, radiotherapy, hormonal manipulation, and novel therapeutic approaches, such as anti-angiogenic drugs. Diffusion-weighted MRI can detect tumor response to chemotherapy quantitatively, sensitively, and early in the treatment regimen. While DCE-MRI provides information regarding tumor vasculature, ADCw is sensitive to cellular volume fractions (cellularity). Because they image different markers of response, DCE- and DW-MRI may show differences in amplitude and timing of response. Hence, these techniques are complementary and could be combined in experimental studies. As DCE-MRI is noninvasive, the tumor can be monitored longitudinally over a period of time to study the changes in tumor vascularity occurring during growth and alterations induced by various kinds of therapy. Initial results in the clinic using the low-molecular-weight contrast agent Gd-DTPA indicate that DCE-MRI is useful for both diagnosis and prognosis.
- Morse, D. L., Payne, C. M., Jennings, D. L., Xia, G., Gillies, R. J., Galons, J. P., & Day, S. E. (2007). MRI-measured water mobility increases in response to chemotherapy via multiple cell-death mechanisms.. NMR in biomedicine, 20(6), 602-14. doi:10.1002/nbm.1127More infoNumerous pre-clinical and clinical reports have demonstrated that the MRI-measured apparent diffusion coefficient of water (ADC) increases early in the response to a wide variety of anti-cancer therapies. It has been proposed that this increase in ADC generally results from an increase in the tumor extracellular volume fraction leading to a greater degree of unrestricted water motion. Furthermore, an increase in extracellular volume has been ascribed to the cell shrinkage that occurs early in the process of programmed cell death. However, other modes of death can be initiated soon after beginning therapy. These other modes of death include mitotic catastrophe and necrosis, and may also involve changes in the fraction of water with unrestricted motion. This work examines whether MRI-measured ADC is altered in response to therapies that induce cell death via non-apoptotic mechanisms and correlates ADC changes with cell death modalities regionally within the tumor. Apoptotic responses were limited to the tumor periphery in apoptosis-proficient tumors. Apoptosis was not observed in deficient tumors. Mitotic catastrophe was observed after treatment at the periphery and deeper into the tumor. Necrosis was the predominant response in the center of the tumor. ADC changes were moderate in the periphery and larger in the center. The results indicate that early and significant changes in ADC can occur in concert with mitotic catastrophe and lytic necrosis in the absence of apoptosis. Hence, changes in ADC may be a generalized measure of cytotoxic response to chemotherapy.
- Jagadish, B., Galons, J. P., Trouard, T. P., Raghunand, N., Mash, E. A., Jagadish, B., & Gillies, R. J. (2006).
Redox-sensitive contrast agents for MRI based on reversible binding of thiols to serum albumin.
. Magnetic resonance in medicine, 55(6), 1272-80. doi:10.1002/mrm.20904More infoDOTA-based complexes of gadolinium (Gd) bearing a thiol moiety on a propyl or hexyl arm were synthesized. It was hypothesized that these complexes would form reversible covalent linkages with human serum albumin (HSA), which contains a reactive thiol at cysteine-34. The binding constant of the hexyl complex to HSA was measured to be 64 mM(-1) and decreased to 17, 6.1, and 3.6 mM(-1) in the presence of 0.5, 1, and 2 mM homocysteine, respectively. The binding constant of the propyl complex to HSA was significantly lower (5.0 mM(-1)) and decreased to 2.0, 1.5, and 0.87 mM(-1) in the presence of 0.5, 1, and 2 mM homocysteine, respectively. The longitudinal water-proton relaxivities of the hexyl and propyl complexes at 37 degrees C and 4.7 T were 2.3 and 2.9 mM(-1) s(-1), respectively, in saline. The relaxivities of the HSA-bound forms of the hexyl and propyl complexes were calculated to be 5.3 and 4.5 mM(-1) s(-1), respectively. The in vivo pharmacokinetics of both thiol complexes were altered by a chase of homocysteine but not saline, while the washout of GdDTPA was unaffected by either chase. Such redox-sensitive reversible binding of Gd complexes to plasma albumin can be exploited for imaging tissue redox and the blood-pool by MRI. - Galons, J. P., Trouard, T. P., Lope-piedrafita, S., Gillies, R. J., Divijak, J. L., & Corum, C. A. (2005).
Uncovering of intracellular water in cultured cells.
. Magnetic resonance in medicine, 54(1), 79-86. doi:10.1002/mrm.20565More infoThe complexity of biologic tissues, with multiple compartments each with its own diffusion and relaxation properties, requires complex formalisms to model water signal in most magnetic resonance imaging or magnetic resonance spectroscopy experiments. In this article, we describe a magnetic susceptibility-induced shift in the resonance frequency of extracellular water by the introduction of a gadolinium contrast agent to medium perfusing a hollow fiber bioreactor. The frequency shift of the extracellular water (+185 Hz at 9.4 T) uncovers the intracellular water and allows direct measurement of motional and relaxation properties of the intracellular space. The proposed method provides a unique tool for understanding the mechanisms underlining diffusion and relaxation in the intracellular space. - Henderson, L. A., Richard, C. A., Macey, P. M., Macey, P. M., Runquist, M. L., Yu, P. L., Harper, R. M., Harper, R. M., & Galons, J. P. (2004).
Functional magnetic resonance signal changes in neural structures to baroreceptor reflex activation.
. Journal of applied physiology (Bethesda, Md. : 1985), 96(2), 693-703. doi:10.1152/japplphysiol.00852.2003More infoThe sequence of neural responses to exogenous arterial pressure manipulation remains unclear, especially for extramedullary sites. We used functional magnetic resonance imaging procedures to visualize neural responses during pressor (phenylephrine) and depressor (sodium nitroprusside) challenges in seven isoflurane-anesthetized adult cats. Depressor challenges produced signal-intensity declines in multiple cardiovascular-related sites in the medulla, including the nucleus tractus solitarius, and caudal and rostral ventrolateral medulla. Signal decreases also emerged in the cerebellar vermis, inferior olive, dorsolateral pons, and right insula. Rostral sites, such as the amygdala and hypothalamus, increased signal intensity as arterial pressure declined. In contrast, arterial pressure elevation elicited smaller signal increases in medullary regions, the dorsolateral pons, and the right insula and signal declines in regions of the hypothalamus, with no change in deep cerebellar areas. Responses to both pressor and depressor challenges were typically lateralized. In a subset of animals, barodenervation resulted in rises and falls of blood pressure that were comparable to these resulting from the pharmacological challenges but different regional neural responses, indicating that the regional signal intensity responses did not derive from global perfusion effects but from baroreceptor mediation of central mechanisms. The findings demonstrate widespread lateralized distribution of neural sites responsive to blood pressure manipulation. The distribution and time course of neural responses follow patterns associated with early and late compensatory reactions. - Reiman, E. M., Galons, J. P., Valla, J., Trouard, T. P., Reiman, E. M., Lin, L., Hicks, C., He, T., He, J., Hauss-wegrzyniak, B., Chen, K., & Alexander, G. E. (2004).
P2-148 Template-based region of interest strategies for measuring ventricular volume in mouse brain MR images: empirical validation with pharmaceutical-induced ventricular increases
. Neurobiology of Aging, 25, S267. doi:10.1016/s0197-4580(04)80895-9 - Reiman, E. M., Galons, J. P., Wenk, G. L., Valla, J., Trouard, T. P., Stevenson, G. D., Reiman, E. M., Hicks, C., He, T., Hauss-wegrzyniak, B., Chen, K., & Alexander, G. E. (2004).
P2-192 The computation of mannitol-induced changes in mouse brain volume using sequential MRI and an iterative principal component analysis
. Neurobiology of Aging, 25, S283. doi:10.1016/s0197-4580(04)80938-2 - Galons, J. P., Erickson, R. P., Trouard, T. P., Guo, J., Gillies, R. J., & Erickson, R. P. (2003).
Magnetization transfer contrast imaging in Niemann pick type C mouse liver.
. Journal of magnetic resonance imaging : JMRI, 18(3), 321-7. doi:10.1002/jmri.10404More infoTo investigate livers of mice afflicted with Niemann Pick type C (NP-C) disease using magnetization transfer contrast (MTC) imaging and to test the hypothesis that the MT ratio reproducibly changes during disease progression..NP-C is a heritable defect of lipid metabolism that results in the accumulation of unesterified cholesterol and gangliosides in virtually all cells. Symptoms predominate in brain and liver, which have high endogenous rates of lipid turnover. It is fatal to children, usually early in the second decade of life. Previous work has shown that the efficiency of magnetization transfer (MT) can be affected by cholesterol and collagen in tissues. The MT ratio (MTR) was calculated and compared during growth and therapy of diseased and control mice..Significant differences in the MTR were observed between livers of diseased and control mice. These ratios were consistent with collagen deposition associated with fibrosis, and not the accumulation of unesterified cholesterol in this organ..These results indicate that MTC imaging may have clinical potential for monitoring progression and therapy in NP-C disease. - Galons, J. P., Morse, D. L., Jennings, D. R., & Gillies, R. J. (2003).
Diffusion-weighted MRI and response to anti-cancer therapies
. Israel Journal of Chemistry, 43(1-2), 91-101. doi:10.1560/gj5m-pp8r-ghub-vuupMore infoIn oncology practice, longitudinal studies are routinely conducted to monitor the size and enhancement of tumors in cancer patients undergoing therapy. Imaging protocols typically use gadolinium-enhanced T 1 -weighted images or T 2 -weighted images from which tumor size is inferred and tumor response estimated. The past few years have also seen the emergence of diffusion-weighted magnetic resonance imaging (DWMRI) as a potential alternative to monitor therapeutic response (Kauppinen, R.A., NMR Biomed. 2002, 15, 6). The attractiveness of DWMRI resides in its ability to detect local microstructural changes associated with treatment long before their effects are translated into effective size changes. Damage to cell membrane integrity, changes in viscosity, and/or relative size of intra- vs. extracellular compartments all translate into changes in the apparent diffusion coefficient of tumor water measured by DWMRI. This dependence makes DWMRI a particularly sensitive method to detect response to a wide variety of chemotherapeutic agents. This review will focus on the emerging role of DWMRI to monitor the response of tumors to anti-cancer chemotherapies. - Galons, J. P., Reiman, E. M., Valla, J., Reiman, E. M., Lin, L., He, J., Hauss-wegrzyniak, B., Chen, K., & Alexander, G. E. (2003).
Construction of mouse brain MRI templates using SPM 99
. IFAC Proceedings Volumes, 36(15), 113-118. doi:10.1016/s1474-6670(17)33484-5More infoAbstract In order to compare brain-imaging measurements from different subjects, brainmapping algorithms are commonly used to register individual brain onto a standardized brain template. In this study, SPM99 is used to construct a spatially standardized template consisting of several spatially standardized high-resolution, T 2 -weighted mouse brain MRI's, and the global precision and local accuracy of the proposed spatial deformation strategy is evaluated. This study provides a foundation for the generation of statistical brain maps from mouse brain images. - Henderson, L. A., Yu, P. L., Frysinger, R. C., Bandler, R., Harper, R. M., Harper, R. M., & Galons, J. P. (2002).
Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging.
. Journal of applied physiology (Bethesda, Md. : 1985), 92(1), 331-42. doi:10.1152/jappl.2002.92.1.331More infoWe examined the sequence of neural responses to the hypotension, bradycardia, and apnea evoked by intravenous administration of 5-hydroxytryptamine (serotonin). Functional magnetic resonance imaging signal changes were assessed in nine isoflurane-anesthetized cats during baseline and after a bolus intravenous low dose (10 microg/kg) or high dose (20-30 microg/kg) of 5-hydroxytryptamine. In all cats, high-dose challenges elicited rapid-onset, transient signal declines in the intermediate portion of the solitary tract nucleus, caudal midline and caudal and rostral ventrolateral medulla, and fastigial nucleus of the cerebellum. Slightly delayed phasic declines appeared in the dentate and interpositus nuclei and dorsolateral pons. Late-developing responses also emerged in the solitary tract nucleus, parapyramidal region, periaqueductal gray, spinal trigeminal nucleus, inferior olivary nucleus, cerebellar vermis, and fastigial nucleus. Amygdala and hypothalamic sites showed delayed and prolonged signal increases. Intravenous serotonin infusion recruits cerebellar, amygdala, and hypothalamic sites in addition to classic brain stem cardiopulmonary areas and exhibits site-specific temporal patterns. - Raghunand, N., Galons, J. P., Jennings, D. R., Trouard, T. P., Raghunand, N., Marshall, J. R., Jennings, D. L., Hatton, B. N., Guo, J., & Gillies, R. J. (2002).
Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI.
. Neoplasia (New York, N.Y.), 4(3), 255-62. doi:10.1038/sj.neo.7900225More infoFor many anticancer therapies, it would be desirable to accurately monitor and quantify tumor response early in the treatment regimen. This would allow oncologists to continue effective therapies or discontinue ineffective therapies early in the course of treatment, and hence, reduce morbidity. This is especially true for second-line therapies, which have reduced response rates and increased toxicities. Previous works by others and ourselves have shown that water mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI), increases early in tumors destined to respond to therapies. In the current communication, we further characterize the utility of DW-MRI to predict response of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting. The current data illustrate that tumor volumes and secreted prostate-specific antigen both respond strongly to docetaxel in a dose-responsive manner, and the apparent diffusion coefficient of water (ADC(w)) increases significantly by 2 days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram analyses. Our results indicate that DW-MRI can be used for early detection of prostate carcinoma xenograft response to docetaxel chemotherapy. - Hauss-wegrzyniak, B., Galons, J. P., & Wenk, G. L. (2000). Quantitative volumetric analyses of brain magnetic resonance imaging from rat with chronic neuroinflammation.. Experimental neurology, 165(2), 347-54. doi:10.1006/exnr.2000.7469More infoBrain inflammation may have a pathogenic role in many neurodegenerative diseases, including Alzheimer's disease. In the present study, we investigated the effects of chronic neuroinflammation upon anatomical changes in two regions of interest in the temporal lobe using high-resolution magnetic resonance imaging techniques. We show that chronic infusion of lipopolysaccharide into the fourth ventricle for 4 consecutive weeks enlarged the lateral ventricles and significantly decreased the size of the hippocampal formation and the temporal lobe region. These changes are comparable to those observed in humans during the early stages of Alzheimer's disease.
- Galons, J. P., Taylor, C. W., Paine-murrieta, G. D., Gillies, R. J., & Altbach, M. I. (1999).
Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging.
. Neoplasia (New York, N.Y.), 1(2), 113-7. doi:10.1038/sj.neo.7900009More infoAn important goal in cancer chemotherapy is to sensitively and quantitatively monitor the response of individual patients' tumors to successful, or unsuccessful, therapy so that regimens can be altered iteratively. Currently, tumor response is monitored by frank changes in tumor morphology, yet these markers take long to manifest and are not quantitative. Recent studies suggest that the apparent diffusion coefficient of water (ADCw), measured noninvasively with magnetic resonance imaging, is sensitively and reliably increased in response to successful CTx. In the present study, we investigate the combination chemotherapy response of human breast cancer tumor xenografts sensitive or resistant to Paclitaxel by monitoring changes in the ADCw. Our results indicate that there is a clear, substantial, and early increase in the ADCw after successful therapy in drug sensitive tumors and that there is no change in the ADCw in p-glycoprotein-positive tumors, which are resistant to Paclitaxel. The mechanism underlying these changes is unknown yet is consistent with apoptotic cell shrinkage and a concomitant increase in the extracellular water fraction. - Raghunand, N., Galons, J. P., Sluis, R. V., Raghunand, N., Gillies, R. J., Cerd�n, S., Cerdan, S., Bhujwalla, Z. M., Ballesteros, P., & Alvarez, J. (1999).
In vivo imaging of extracellular pH using 1H MRSI.
. Magnetic resonance in medicine, 41(4), 743-50. doi:10.1002/(sici)1522-2594(199904)41:4<743::aid-mrm13>3.0.co;2-zMore infoTumor pH is physiologically important since it influences a number of processes relevant to tumorigenesis and therapy. Hence, knowledge of localized pH within tumors would contribute to understanding these processes. The destructiveness, poor spatial resolution, and poor signal-to-noise ratio (SNR) of current technologies (e.g., microelectrodes, 31P magnetic resonance spectroscopy) have limited such studies. An extrinsic chemical extracellular pH (pHe) probe is described that is used in combination with 1H magnetic resonance spectroscopic imaging to yield pHe maps with a spatial resolution of 1 x 1 x 4 mm3. The principle of the technique is demonstrated on a phantom. Further data are shown to demonstrate its application in vivo, and results agree with previously reported pH values. The accuracy of the reported pH measurements is - Galons, J. P., Gmitro, A. F., Trouard, T. P., Lien, Y. H., & Gmitro, A. F. (1996).
Hemodialysis increases apparent diffusion coefficient of brain water in nephrectomized rats measured by isotropic diffusion-weighted magnetic resonance imaging.
. The Journal of clinical investigation, 98(3), 750-5. doi:10.1172/jci118847More infoThe nature of brain edema in dialysis disequilibrium syndrome (DDS) was investigated by diffusion-weighted magnetic resonance imaging (DWI). DWI was performed on normal or bilaterally nephrectomized rats before, and immediately after, hemodialysis. Hemodialysis was performed with a custom-made dialyzer (surface area 150 cm2) against a bicarbonate-buffered bath for 90 min with or without 70 mM urea. Hemodialysis with non-urea bath decreased plasma urea by 21 mM, and plasma osmolality by 22 mosmol/kg H2O, and increased brain water content by 8.0% (all < 0.05), while hemodialysis with urea bath did not affect plasma urea, osmolality, or brain water content. Three sets of axial DWI images of the brain were obtained at different gradient weighing factors with an in-plane resolution of 0.39 mm2. The apparent diffusion coefficient (Dapp) of the brain water was not affected by bilateral nephrectomy, or by hemodialysis in normal rats. In nephrectomized rats, brain Dapp was significantly increased after dialysis with non-urea bath (1.15 +/- 0.08 vs 0.89 +/- 0.07 x 10(-9)m2/sec, P < 0.01). No significant changes of brain water Dapp could be observed after dialysis with urea bath. The increased Dapp associated with DDS indicates that brain extracellular water increases and/or intracellular water decreases after hemodialysis. Our results strongly suggest that the brain edema induced by hemodialysis in uremic rats is due to interstitial edema rather than cytotoxic edema. Furthermore, our results support a primary role for the "reverse urea effect" in the pathogenesis of brain edema in DDS.DWI may be a useful diagnostic tool for DDS in patients with end-stage renal disease. - Gillies, R. J., Galons, J. P., Mcgovern, K. A., Scherer, P. G., Lien, Y. H., Job, C., Ratcliff, R., Chapa, F., Cerdan, S., & Dale, B. E. (1993). Design and application of NMR-compatible bioreactor circuits for extended perfusion of high-density mammalian cell cultures.. NMR in biomedicine, 6(1), 95-104. doi:10.1002/nbm.1940060115More infoMR spectroscopy of cultured cells allows non-invasive analyses of the metabolism of cells with specific phenotypes under defined conditions. This technique can be used to investigate the intracellular metabolism of cells or extended to critically evaluate phenomena observed by in vivo MRS. In this paper, a cell maintenance system is described which allows MR analyses with unparalleled spectral resolution, S/N and stability. This system consists of a 25 mm diameter hollow fiber bioreactor and a supporting circuit. The hollow fiber reactor was chosen because it yields a large filling factor which can be perfused through defined volumes. The fibers were 300 microns diameter microporous (0.2 micron) cellulose acetate/cellulose nitrate membranes with high porosity, which allow bulk convective flow throughout the extracapillary space. This flow (Starling flow) is necessary to disrupt steady-state gradients in substrates and waste products. In many respects, the design of the supporting circuit is more important than the bioreactor itself, since it provides the reactor with the proper chemical and physical environment. Hence, this circuit can be applied to a variety of bioreactor configurations. The circuit consists of a hollow fiber oxygenator and a bleed-and-feed system housed in a temperature-controlled cabinet. Culture of mammalian cells in this reactor yields 31P spectra which have excellent spectral and temporal resolution. At confluence, endogenous 31P line widths were typically < 10 Hz (at 162 MHz) and well resolved spectra were obtained in < 30 s.
- Fantini, J., Vion-dury, J., Cozzone, P. J., Canioni, P., & Galons, J. P. (1990). Effect of VIP on the glycogen metabolism of human colon adenocarcinoma cells studied by 13C nuclear magnetic resonance spectroscopy.. International journal of cancer, 45(1), 168-73. doi:10.1002/ijc.2910450130More infoMetabolic pathways of glucose utilization have been investigated in a human colon adenocarcinoma cell line (HT29) using carbon-13 Nuclear Magnetic Resonance spectroscopy. HT29 cells were adapted to grow on a polystyrene beaded microcarrier and were perfused when attached to the beads in a specially designed NMR cell. Abnormalities in carbohydrate metabolism already observed in several cancer cells were studied in HT29 cells fed with (1-13C)-enriched glucose. The cells were first perfused with a glucose-free medium for 2 h in order to deplete the intracellular store of glycogen, and they were subsequently perfused with a medium containing enriched glucose at an initial concentration of 5.5 mM. Sequential 13C-NMR spectra, recorded at 100.5 MHz (5 min accumulation), show that HT29 cells were able to utilize glucose through the glycolytic pathway while storing glucose as glycogen (glucose was utilized at a rate of 3.9 mumol/mg protein/hr). The glycolytic activity determined by the amount of lactic acid produced was 4.6 microns/mg protein/hr, corresponding to the formation of 1.2 lactic acid per glucose molecule. Glycogen accumulation corresponded to 16 micrograms/mg of protein. Treatment of HT29 with 10 nM vasoactive intestinal peptide (VIP) induced a transient decrease in the level of labelled glycogen to 50% of the initial value. Control level was recovered 12 min after VIP loading.
- Canioni, P., Desmoulin, F., Bernard, M., Fontanarava, E., Pusel, J. M., Galons, J. P., & Cozzone, P. J. (1984). Application de la résonance magnétique nucléaire à l'étude de cellules et d'organes isolés. Biochemistry.More infoApport de la RMN du phosphore 31 et du carbone 13: identification des composes phosphoryles du metabolisme energetique, mesure du pH intracellulaire, determination de flux metaboliques, analyse de la mobilite des metabolites
Proceedings Publications
- Keerthivasan, M. B., Blew, D., Galons, J., Martin, D. R., Bilgin, A., & Altbach, M. I. (2018, June). Characterization of Abdominal Neoplasms using a Fast T2 Mapping Radial TSE Technique. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Altbach, M. I., Bilgin, A., Martin, D. R., Galons, J., & Keerthivasan, M. B. (2021). Multi-component T2 Modeling for Improved Characterization of Abdominal Neoplasms. In Annual Meeting of the International Society for Magnetic Resonance in Medicine.
- Altbach, M. I., Bilgin, A., Martin, D. R., Galons, J., Umapathy, L., & Keerthivasan, M. B. (2021). Efficient T2 mapping of the Abdomen with low SAR Variable Flip Angle Radial Turbo Spin Echo. In Annual Meeting of the International Society for Magnetic Resonance in Medicine.
- Hutchinson, E. B., Trouard, T. P., Does, M., Harkins, K., & Galons, J. (2020, April). Quantitative myelin imaging in the ferret brain for traumatic brain injury research. In International Society for Magnetic Resonance in Medicine.
- Keerthivasan, M. B., Li, Z., Galons, J., Johnson, K., Kalb, B. T., Martin, D. R., Bilgin, A., & Altbach, M. I. (2019, May). Characterization of Abdominal Neoplasms using a Fast Inversion Recovery Radial SSFP T1 Mapping Technique. In Annual Meeting of the ISMRM, Montreal, QC, Canada.
- ,, D., Anilkumar, A., ,, T., Altbach, M. I., Galons, J. P., Thomson, C., Stopeck, A., & Huang, C. (2018, Spring). Automated breast segmentation with high reproducibility of MR-based breast density measurement. In International Society Magnetic Resonance in Medicine.
- Altbach, M. I., Bilgin, A., Martin, D. R., Galons, J., Blew, D., & Keerthivasan, M. B. (2018, June). Characterization of Abdominal Neoplasms using a Fast T2 Mapping Radial TSE Technique. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Altbach, M. I., Johnson, K., Bilgin, A., Martin, D. R., Galons, J., Keerthivasan, M. B., Unger, W. D., Saranathan, M., & Pandey, A. (2018, June). Quantifying hepatic fibrosis using 3D radial golden angle stack-of stars acquisition and a dual input two compartment model. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Bilgin, A., Altbach, M. I., Martin, D. R., Unger, W. D., Galons, J., Keerthivasan, M. B., & Umapathy, L. (2018, June). A Comparison of Deep Learning Convolutional Neural Networks for Liver Segmentation in Radial Turbo Spin Echo Images. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Ding, J., Stopeck, A., Gao, Y., Marron, M., Wertheim, B., Altbach, M. I., Galons, J. P., Roe, D., Maskarinec, G., Thomson, C., Thompson, P., & Huang, C. (2018, June). A MRI-based breast density measure which is directly comparable to mammographic density. In ISMRM Paris, France.
- Li, Z., Bilgin, A., Johnson, K., Galons, J., Saranathan, M., Martin, D. R., & Altbach, M. I. (2018, June). Rapid multi-slice abdominal T1 mapping with IR-radSSFP. In 2018 Meeting of the International Society for Magnetic Resonance in Medicine.
- Galons, J. P., Marron, M. T., Stopeck, A., Rodriguez, J. J., Thomson, C. A., Rosado-toro, J. A., Rodriguez, J. J., Marron, M. T., Barr, T., & Altbach, M. I. (2013).
Automated segmentation of breast fat-water MR images using empirical analysis
. In 2013 IEEE International Conference on Acoustics, Speech and Signal Processing, 1018-1022.More infoBreast density (BD) has been advocated as a risk factor for the development of breast cancer. BD is typically measured from mammograms. However for longitudinal studies of patients at risk, BD can be better assessed using MRI due to the lack of ionizing radiation and the 3D capabilities of the technique. A fat-water (FW) imaging technique called RAD-GRASE was developed to acquire images of the entire breast in a few minutes and can generate fat-fraction maps, which can be used to assess BD. The time consuming manual segmentation on ~19 slices per exam can be challenging. In this paper, we present a method to automatically segment the breast tissue in FW images and yield FW profiles of the region of interest (ROIs). - Reiman, E. M., Reiman, E. M., Galons, J. P., Valla, J., Reiman, E. M., Lin, L., He, J., Hauss-wegrzyniak, B., Chen, K., & Alexander, G. E. (2005).
MRI Template and Atlas Toolbox for the C57BL/6J Mouse Brain
. In Conference Proceedings. 2nd International IEEE EMBS Conference on Neural Engineering, 2005., 6-8.More infoIn order to compare brain-imaging measurements from different subjects, brain-mapping algorithms are commonly used to register individual brain onto a standardized brain atlas. In this study, SPM99 was used to linearly and nonlinearly coregister a spatially standardized T2-weighted template of C57BL/6J to the atlas by Paxinos and Franklin (2001), local accuracy of between atlas and template was evaluated, and a toolbox was developed. This study provides a foundation for the region of interest analysis for mouse brain images - Veress, A. I., Weiss, J. A., Gillies, R. J., Bowden, A. E., Galons, J. P., & Rabbitt, R. D. (2002). Deformable Image Registration of Mouse Brain MRI Data Using Hyperelastic Warping. In Advances in Bioengineering, 195-196.More infoQuantification of time-dependent changes in three-dimensional morphology of brain structures and neural pathways is a fundamental requirement in studies of neurodevelopment, remodeling and progression of neurological diseases [1]. However, local measures of this kind are extremely difficult due to a lack of clear fiducials. Our motivation to develop a reliable technique to quantify time-dependent changes in neuroanatomy originated with the problem of tracking progression of Niemann-Pick disease type C (NP-C), a heritable disease that causes alterations in brain development [2].Copyright © 2002 by ASME
Presentations
- Witte, M. H., Erickson, R. P., & Barnes, T. (2023, Fall). Non-Invasive Peripheral and Central Lymphatic Imaging in Neonates and Young Children with Lymphatic Disorders. 29th World Congress of Lymphology. Genoa, Italy: International Society of Lymphology.
- Witte, M. H., Galons, J., Saranathan, M., Kalb, B. T., Moedano, L., & Seckeler, M. (2019, September). Non-Contrast MR Lymphology of Rare Central Lymphatic Abnormalities. International Society of Lymphology XXVII World Congress 2019. Buenos Aires, Argentina.
- Galons, J. (2018, Winter). Quantitative MRI tools for clinical assessment of kidney function and staging of liver fibrosis. Medical Imaging Grand Round. University of Arizona.
- Li, Z., Johnson, K., Galons, J. P., Saranathan, M., Martin, D., & Altbach, M. (2018, June). Rapid multi-slice abdominal T1 mapping with high spatial and temporal resolution using an inversion recovery radial steady-state free precession (IR-radSSFP) technique. ISMRM, Paris, France.
- Pandey, A., Galons, J. P., Johnson, K., Martin, D., Altbach, M., Bilchik, A. J., & Saranathan, M. (2017, 2017). Glomerular Filtration rate estimation in vivo using 3D radial MRI and a novel multiresolution reconstruction technique. Proceedings of ISMRM.
- Pandey, A., Min, C., Li, Z., Johnson, K., Purvis, L., Harland, D., Papas, K., Sharma, P., Martin, D., Saranathan, M., & Galons, J. P. (2017, 2017). An MR Compatible Kidney Perfusion System to Assess Kidney Function and Organ Preservation.. Proceedings of ISMRM, Hawai.
- Galons, J. (2015, May). Autocorrelation Analysis of Hepatic Fibrosis on MRI. ISMRM Annual Meeting. Toronto, Canada.
Poster Presentations
- Chow, H., Algotar, A., Martinez, J. A., Trujillo, J., Altbach, M. I., Thomson, C. A., Galons, J., Huang, C., Guillen, J., Roe, D., Centuori, S. M., Chalasani, P., Villa Guillen, D., Tapia, E., & Pinto, L. (2021, November). A randomized controlled trial of metformin in women with components of metabolic syndrome: Intervention feasibility and effects on breast density and adiposity. SABCS.
- Chow, H., Algotar, A., Altbach, M. I., Galons, J., Roe, D., Thomson, C. A., Guillen-Rodriguez, J. M., Martinez, J. A., Chalasani, P., Villa Guillen, D. E., Tapia, E. O., & Trujillo, J. (2018, Fall). Abstract: Phase II clinical study of metformin for breast cancer prevention. UACC Scientific Retreat. UACC Scientific Retreat. Tucson, AZ.
- Ding, J., Thompson, P., Gao, Y., Marron, M., Wertheim, B., Altbach, M., Galons, J. P., Roe, D., Wang, F., Mascarinec, G., Thomson, C., Stopeck, A., & Huang, C. (2017, 2017). Accurate and Reliable Fat-Water MRI Breast Density Measurements. Proceedings of ISMRM, Hawai.
- Keerthivasan, M., Saranathan, M., Bilgin, A., Galons, J. P., Martin, D., & Altbach, M. (2017, 2017). High-resolution 3D T2 mapping using a stack-of-stars radial FSE pulse sequence. ISMRM. Hawai, USA.
- Keerthivasan, M., Saranathan, M., Galons, J. P., Martin, D., Bilgin, A., & Altbach, M. (2017, 2017). Variable Flip Angle Radial Turbo Spin Echo Technique for Abdominal T2 Mapping. Proceedings of ISMRM, Hawai. Hawai.
- Umapathy, L., Brand, J., Galons, J. P., Furenlid, L., Martin, D. R., & Altbach, M. (2017, 2017). Wavelet based Texture Analysis of Liver Fibrosis in Delayed Phase Gadolinium-Enhanced T1-weighted in vivo Images. Proceedings of ISMRM, Hawai.
- Ding, J., Thompson, P. A., Wertheim, B. C., Roe, D. J., Marron, M. T., Altbach, M. I., Galons, J., Wang, F., Thomson, C. A., Huang, C., & Stopeck, A. (2017, April). Abstract: Early detection of changes in breast density using fat-water decomposition MRI in women on tamoxifen. International Society for Magnetic Resonance in Medicine. Honolulu, HI: ISMRM.
- Hagio, T., Galons, J., Thompson-Carino, P. A., Stopeck, A. T., Thomson, C. A., Chalasani, P., Squire, S. W., Marron, M. T., & Altbach, M. I. (2016, Spring). T2w mapping in breast density for differentiating tissue composition. International Society for Magnetic Resonance in Medicine. Singapore.
- Rosado-Toro, J. A., Barr, T., Galons, J., Marron, M. T., Stopeck, A. T., Thomson, C. A., Thompson, P., Carroll, D., Wolf, E., Altbach, M. I., Rodriguez, J. J., Rosado-Toro, J. A., Barr, T., Galons, J., Marron, M. T., Stopeck, A. T., Thomson, C. A., Thompson, P., Carroll, D., , Wolf, E., et al. (2015, May 30 – June 5). Automatic Segmentation of Breast Images Using Clustering and Dynamic Programming. ISMRM 23rd Annual Meeting & Exhibition. Toronto, Canada: Intl. Society for Magnetic Resonance in Medicine.