Research
Patients with similar tumour types can show markedly different responses to the same therapy. The development of new treatments would benefit, therefore, from the introduction of imaging methods that allow an early assessment of treatment response in individual patients, allowing rapid selection of the most effective treatment for a specific patient (Brindle, Nat. Rev. Cancer 2008; 8: 1).
We have been developing novel and potentially clinically applicable imaging methods for detecting the early responses of tumours to treatment. This has included a targeted imaging agent for detecting tumour cell death, which has been patented and which we are planning to take to the clinic, and a new magnetic resonance method for imaging tumour cell metabolism.
Through a partnership with GE Healthcare we have developed nuclear spin hyperpolarization as a novel tool for imaging tissue metabolism in vivo. Nuclear spin polarization offers enormous gains in sensitivity, as much as 10,000 – 100,000x, which makes it possible not only to image the distribution of isotopically-labelled cellular metabolites in vivo, but also their enzymatic transformation into other species. This has provided us with more sensitive ways to detect tumour responses to treatment and, with some substrates, is giving new insights into tumour metabolism in vivo. We have now translated this technique to the clinic and have conducted studies in breast, glioma, ovarian, kidney and pancreatic cancer patients.
Publications
MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter. Schilling, F., Ros, S., Hu, D.-E., D'Santos, P., McGuire, S., Mair, R., Wright, A. J., Mannion, E., Franklin, R. J. M., Neves, A. A., and Brindle, K. M. (2017) Nature Biotechnology 35, 75–80.
Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C labeled glucose. Rodrigues, T. B., Serrao, E. M., Kennedy, B. W. C., Hu, D., Kettunen, M. I. and Brindle, K. M. (2014) Nature Med 20, 93-97.
Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: Vitamin C as a probe for imaging redox status in vivo. Bohndiek, S. E., Kettunen, M. I., Hu, D., Kennedy, B. W. C., Boren, J., Gallagher, F. A., Brindle, K. M. (2011) J. Amer. Chem. Soc. 133, 11795-11801.
Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate
is a marker of cell necrosis and treatment response in tumors. Gallagher, F.A., Kettunen, M. I., Hu, D.-E., Jensen, R. J., in ‘t Zandt, R., Karlsson, M., Gisselsson, A., Nelson, S. K., Witney, T. H., Bohndiek, S. E., Hansson, G., Peitersen, T., Lerche, M. H., Brindle, K. M. (2009) Proc. Natl Acad. Sci. USA 106, 19801-19806.
Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labeled bicarbonate. Gallagher, F. A., Kettunen, M. I., Day, S. E., Hu, D.-E., Ardenkjær-Larsen, J. H., in ‘t Zandt, R., Jensen, P. R., Karlsson, M., Golman, K., Lerche, M. H., and Brindle, K. M. (2008) Nature 453, 940-943.
Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Day, S. E., Kettunen, M. I., Gallagher, F. A., Hu, D.-E., Lerche, M., Wolber, J., Golman, K., Ardenkjaer-Larsen, J. H., and Brindle, K. M. (2007) Nature Medicine 13, 1382 – 1387.
Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Zhao, M., Beauregard, D. A., Loizou, L., Davletov, B., Brindle, K. M. (2001) Nature Med. 7,1241 - 1244.
Immune-modulating and anti-vascular activities of two xanthenone acetic acid analogues: A comparative study to DMXAA. Barbera, M., Kettunen, M. I., Caputo, A., Hu, D.-E., Gobbi, S., Brindle, K. M., Carrara, M. (2009) Int. J. Oncol. 34, 273-279.
Characterization of image heterogeneity using 2D Minkowski Functionals increases the sensitivity of detection of a targeted MRI contrast agent. Canuto, H. C., McLachlan, C., Kettunen, M. I., Velic, M., Krishnan, A. S., Neves, A. A., de Backer, M., Hu, D. E., Hobson, M. P., Brindle, K. M. (2009) Magn. Reson. Med. 61, 1218-1224.
A comparison between radiolabeled fluorodeoxyglucose uptake and hyperpolarized C-13-labeled pyruvate utilization as methods for detecting tumor response to treatment. Witney, T. H., Kettunen, M. I., Day, S. E., Hu, D. E., Neves, A. A., Gallagher, F. A., Fulton, S. M., Brindle, K. M. (2009) Neoplasia 11, 574-582.
Biomedical applications of hyperpolarized 13C magnetic resonance imaging. Gallagher, F. A., Kettunen, M. I., Brindle, K. M. (2009) Prog. NMR Spectrsoc. 55, 285–295.
Magnetization transfer measurements of exchange between hyperpolarized [1-13C]pyruvate and [1-13C]lactate in a murine lymphoma. Kettunen, M. I., Hu, D.-E., Witney, T. H., McLaughlin, R., Gallagher, F. A., Bohndiek, S. E., Day, S. E., Brindle, K. M. (2010) Magn. Reson. Med. 63, 872-880
Comparison of the C2A Domain of Synaptotagmin-I and Annexin-V as probes for detecting cell death. Alam, I. S., Neves, A. A., Witney, T. H., Boren, J., and Brindle, K. M. (2010) Bioconjugate Chem. 21, 884–891.
Imaging and 'omic' methods for the molecular diagnosis of cancer. Bohndiek, S. E., Brindle, K. M. (2010) Expert Rev Mol Diagn 10, 417-434.
Imaging tumour cell metabolism using hyperpolarized 13C magnetic resonance spectroscopy. Witney, T. H., and Brindle, K. M. (2010) Biochem. Soc. Trans. 38, 1220–1224.
Detecting treatment response in a model of human breast adenocarcinoma using hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate. Witney, T. H., Kettunen, M. I., Hu, D.-E., Gallagher, F. A., Bohndiek, S. E., Napolitano, R., and Brindle, K. M. (2010) Brit. J. Cancer. 103, 1400-1406.
Detecting tumor response to a vascular disrupting agent using hyperpolarized 13C magnetic resonance spectroscopy. Bohndiek, S. E., Kettunen, M. I., Hu, D.-E., Witney, T. H., Kennedy, B. W. C., Gallagher, F. A., and Brindle, K. M. (2010) Molec. Cancer Ther. 9, 3278-3288.
Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1-13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Day, S. E., Kettunen, M. I., Cherukuri, M. K., Mitchell, J. B., Lizak, M. J., Morris, H. D., Matsumoto, S., Koretsky, A. P., and Brindle, K. M. (2011) Magn. Reson. Med. 65, 557-563
Detection of tumor glutamate metabolism in vivo using 13C magnetic resonance spectroscopy and hyperpolarized [1-13C]glutamate. Gallagher, F. A., Kettunen, M. I., Day, S. E., Hu, D.-E., Karlsson, M., Gisselsson, A., Lerche, M. H., Brindle, K. M. (2011) Magn. Reson. Med. 66, 18-23.
Imaging sialylated tumor cell glycans in vivo. Neves, A. A., Stöckmann, H., Harmston, R. R., Pryor, H. J., Alam, I. S., Ireland-Zecchini, H., Lewis, D. Y., Lyons, S. K., Leeper, F. J., Brindle, K. M. (2011) FASEB J. 25, 2528-2537.
Development and evaluation of new cyclooctynes for cell surface glycan imaging in cancer cells. Stöckmann, H, Neves, A. A., Stairs, S., Ireland-Zecchini, H., Brindle, K. M., Leeper, F. J. (2011) Chem. Sci. 2, 932-936.
(E,E)-1,5-Cyclooctadiene: a small and fast click-chemistry multitalent. Stöckmann, H., Neves, A. A., Day, H. A., Stairs, S., Brindle, K. M., Leeper, F. J. (2011) Chem. Comm. 47, 7203 – 7205.
Kinetic modeling of hyperpolarized 13C label exchange between pyruvate and lactate in tumor cells. Witney, T. H., Kettunen, M. I., Brindle, K. M. (2011) J. Biol. Chem. 286, 24572-24580.
Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy. Brindle, K. M., Bohndiek, S. E., Gallagher, F. A., Kettunen, M. I. (2011) Magn. Reson. Med. 66, 505–519.
Hyperpolarized 13C MRI and PET: In vivo tumor biochemistry. Gallagher, F.A., Bohndiek, S.E., Kettunen, M.I., Lewis, D.Y., Soloviev, D., Brindle, K.M. (2011) J. Nucl. Med. 52, 1333-1336.
Gallagher F.A., Kettunen M.I., Brindle K.M. Imaging pH with hyperpolarized 13C. (2011) NMR in Biomed. 24, 1006-1015.
Exploring isonitrile-based click chemistry for ligation with biomolecules. Stöckmann, H., Neves, A.A., Stairs, S., Brindle, K.M., and Leeper, F.J. (2011) Org. Biomol. Chem. 9, 7303-7305.
Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus. Bird-Lieberman, E. L., Neves, A. A., Lao-Sirieix, P., O’Donovan, M., Novelli, M., Lovat, L. B., Eng, W. S., Mahal, L. K., Brindle, K. M., Fitzgerald, R. C. (2012) Nature Med. 18, 315-321
Probing lactate dehydrogenase activity in tumors by measuring hydrogen/deuterium exchange in hyperpolarized L-[1-13C,U-2H]Lactate. Kennedy, B. W. C., Kettunen, M. I., Hu, D.-E., and Brindle, K. M. (2012) J. Amer. Chem. Soc. 134, 4969−4977.
Hyperpolarized 13C spectroscopy detects early changes in tumor vasculature and metabolism after VEGF neutralization. Bohndiek, S. E., Kettunen, M. I., Hu D. E., Brindle, K.M. (2012) Cancer Res. 72, 854 – 864.
Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation. Boren, J., and Brindle, K. M. (2012) Cell Death and Differentiation 19, 1561–1570.
Direct enhancement of nuclear singlet order by dynamic nuclear polarization (2012) Tayler, M. C. D., Marco-Rius, I., Kettunen, M. I., Brindle, K. M., Levitt, M. H., and Pileio, G. (2012) J. Am. Chem. Soc. 134, 7668−7671.
Magnetic resonance imaging with hyperpolarized [1,4-13C2]fumarate allows detection of early renal acute tubular necrosis. Clatworthy, M.R., Kettunen, M. I., Hu, D.-E., Mathews, R. J., Witney, T. H., Kennedy, B. W. C., Bohndiek, S. E., Gallagher, F. A., Jarvis, L. B., Smith, K. G. C., and Brindle, K. M. (2012) Proc. Natl Acad. Sci. 109, 13374–13379.
Watching tumours gasp and die with MRI: the promise of hyperpolarised 13C MR spectroscopic imaging. Brindle, K. (2012) Brit J. Radiol. 85, 697-708.
What do magnetic resonance-based measurements of Pi -> ATP Flux tell us about skeletal muscle metabolism? Kemp, G. J. and Brindle, K. M. (2012) Diabetes 61, 1927-1934.
Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-13C]Lactate and [1-13C]Pyruvate. Kettunen, M. I., Kennedy, B. W. C., Hu, D.-E. and Brindle, K. M. (2012) Magn Reson. Med. 70, 1200–1209.
Imaging cell surface glycosylation in vivo using “double click” chemistry. Neves, A. A., Stöckmann, H., Wainman, Y. A., Kuo, J. C-H., Fawcett, S., Leeper, F. J. and Brindle, K. M. (2013) Bioconjugate Chem. 24, 934−941. (Cover article).
Metabolic glycan Imaging by isonitrile–tetrazine click chemistry. Stairs, S., Neves, A. A., Stöckmann, H., Wainman, Y. A., Ireland-Zecchini, H., Brindle, K. M. and Finian J. Leeper. (2013) ChemBioChem 14, 1063–1067.
Dual-sugar imaging using isonitrile and azido-based click chemistries. Wainman, Y. A., Neves, A. A., Stairs, S., Stöckmann, H., Ireland-Zecchini, H., Brindle, K. M., and Leeper, F. J. (2013) Org. Biomol. Chem. 11, 7297-7300.
Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment. Larkin, T. J., Canuto, H. C., Kettunen, M. I., Booth, T. C., Hu, D-E., Krishnan, A. S., Bohndiek, S. E., Neves, A. A., McLachlan, C., Hobson, M. P., Brindle, K. M. (2014) Magn. Reson. Med. 71, 402-410.
Quantitation of a spin polarization-induced nuclear Overhauser effect (SPINOE) between a hyperpolarized 13C-labeled cell metabolite and water protons. Marco-Rius, I., Bohndiek, S. E., Kettunen, M. I., Larkin, T. J., Basharat, M., Seeley, C. and Brindle, K. M. (2014) Contrast Media and Mol. Imag. 9, 182-186.
Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse. Marco-Rius, I., Tayler, M. C. D., Kettunen, M. I., Larkin T. J., Timm K. N., Serrao, E. M., Rodrigues, T. B., Pileio, G., Ardenkjaer-Larsen, J. H., Levitt, M. H., Brindle, K. M. (2013) NMR in Biomed. 26, 1696−1704.
Dual-modality gene reporter for in vivo imaging. Patrick, P.S., Hammersley, J., Loizou, L., Kettunen, M.I., Rodrigues, T.B., Hu, D.-E., Tee, S.-S., Hesketh, R., Lyons, S.K., Soloviev, D., Lewis, D.Y., Aime, S., Fulton, S.M., and Brindle, K.M. (2014) Proceedings of the National Academy of Sciences USA. 111, 415–420.
Imaging cell death. Neves, A.A., and Brindle, K.M. (2014) J. Nuc. Med. 55, 1-4.
Versatile and enhanced tumour modelling in mice via somatic cell transduction. Rodriguez, E., Mannion, L., D’Santos, P., Griffiths, M., Arends, M. J., Brindle, K. M., and Lyons, S. K. (2014) J. Pathol. 232, 449–457.
Late imaging with [1-11C]acetate improves detection of tumor fatty acid synthesis with PET. Lewis, D. Y., Boren, J., Shaw, G. L., Bielik, R., Ramos-Montoya, A., Larkin, T. J., Martins, C. P., Neal, D. E., Soloviev, D., and Brindle, K. M. (2014) J Nucl Med 55, 1144–1149.
Oatp1 enhances bioluminescence by acting as a plasma membrane transporter for D-luciferin. Patrick, P. S., Lyons, S. K., Rodrigues, T. B., and Brindle, K. M. (2014) Mol. Imag. Biol. 16, 626-634.
Imaging tumor metabolism using positron emission tomography. Lewis, D. Y., Soloviev, D., Brindle, K. M. (2015) Cancer J. 21, 129 – 136.
13C magnetic resonance spectroscopic imaging of hyperpolarized [1-13C, U-2H5] ethanol oxidation can be used to assess aldehyde dehydrogenase activity in vivo. Dzien, P., Kettunen, M. I., Marco-Rius, I., Serrao, E. M., Rodrigues, T. B., Larkin, T. J., Timm, K. N., and Brindle, K. M. (2015) Magn. Reson. Med., 73, 1733-1740.
Detection of transgene expression using hyperpolarized 13C urea and diffusion-weighted magnetic resonance spectroscopy. Patrick, P. S., Kettunen, M. I., Tee, S.-S., Rodrigues, T. B., Serrao, E., Timm, K. N., McGuire, S., and Brindle, K. M. (2015) Magn. Reson. Med., 73, 1401–1406.
Imaging metabolism with hyperpolarized 13C-labeled cell substrates. Brindle, K. M. (2015) J. Amer. Chem. Soc. 137, 6418 - 6427.
Measurements of carbonic anhydrase activity in vivo using hyperpolarized 13C-magnetic resonance spectroscopy demonstrate its importance in pH regulation. Gallagher, F.A., Sladen H., Kettunen, M.I., Serrao, E.M., Rodrigues, T.B., Wright A., Gill, A., McGuire, S., Booth, T.C., Boren, J., McIntyre, A., Miller, J.L., Lee, S-H., Honess, D., Day, S.E., Hu, D., Howat, W.J., Harris, A.L., Brindle, K.M. (2015) Cancer Res. 75, 4109-4118.
Hyperpolarized [U-2H, U-13C] Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells. Timm, K.N., Hartl, J., Keller, M.A., Hu, D.E., Kettunen, M.I., Rodrigues, T.B., Ralser, M., Brindle, K.M. (2015) Magn. Reson. Med. 74, 1543-1547.
Development of Timd2 as a reporter gene for MRI. Patrick P.S., Rodrigues, T.B., Kettunen, M.I., Lyons, S.K., Neves, A.A., Brindle, K.M. (2016) Magn. Reson. Med. 75, 1697-1707.
Magnetic resonance imaging with hyperpolarized [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model. Serrao, E. M., Kettunen, M. I., Rodrigues, T. B., Dzien, P., Wright, A. J., Gopinathan, A., Gallagher, F. A., Lewis, D. Y., Frese, K. K., Almeida, J., Howat, W. J., Tuveson, D. A., Brindle, K. M. (2016) Gut 65, 465–475.
Imaging glycosylation in vivo by metabolic labeling and magnetic resonance imaging. Neves, A. A., Wainman, Y. A., Wright, A., Kettunen, M. I., Rodrigues, T. B., McGuire, S., Hu, D.-E., Bulat, F., Geninatti Crich, S., Stöckmann, H., Leeper, F. J. and Brindle, K. M. (2016) Angew. Chem. Int. Ed. 55, 1286 –1290
Potential clinical roles for metabolic imaging with hyperpolarized [1-13C]pyruvate. Serrao, E. M., and Brindle, K. M. (2016) Front. Oncol. 6, DOI: 10.3389/fonc.2016.00059.
Detection of colorectal dysplasia using fluorescently labelled lectins. Kuo, J. C. H., Ibrahim, A. E. K., Dawson, S., Parashar, D., Howat, W. J., Guttula, K., Miller, R., Fearnhead, N. S., Winton, D. J., Neves, A. A., Brindle, K. M. (2016) Sci. Rep. 6, DOI: 10.1038/srep24231.
Effects of fasting on serial measurements of hyperpolarized [1-13C]pyruvate metabolism in tumors. Serrao, E. M., Rodrigues, T. B., Gallagher, F. A., Kettunen, M. I., Kennedy, B. W. C., Vowler, S. L., Burling, K. A., and Brindle, K. M. (2016) NMR Biomed. 29, 1048-1055.
13C magnetic resonance spectroscopy measurements with hyperpolarized [1-13C]pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo. Dzien, P., Tee, S. S., Kettunen, M. I., Lyons, S. K., Larkin, T. J., Timm, K. N., Hu, D. E., Wright, A., Rodrigues, T. B., Serrao, E. M., Marco-Rius, I., Mannion, E., D'Santos, P., Kennedy, B. W. C., and Brindle, K. M. (2016) Magn. Reson. Med. 76, 391-401.
The relationship between endogenous thymidine concentrations and F-18 FLT uptake in a range of preclinical tumour models. Heinzmann, K., Honess, D. J., Lewis, D. Y., Smith, D. M., Cawthorne, C., Keen, H., Heskamp, S., Schelhaas, S., Witney, T. H., Soloviev, D., Williams, K. J., Jacobs, A. H., Aboagye, E. O., Griffiths, J. R., and Brindle, K. M. (2016) EJNMMI Res. 6: 63.
Imaging tumor metabolism to assess disease progression and treatment response. Timm, K. N., Kennedy, B. W. C., and Brindle, K. M. (2016) Clinical Cancer Research 22, 5196-5203.
Single shot three-dimensional pulse sequence for hyperpolarized 13C MRI. Wang, J. Z., Wright, A. J., Hu, D-E., Hesketh, R., and Brindle, K. M. (2017) Magn. Reson. Med. 77, 740-752.
Assessing oxidative stress in tumors by measuring the rate of hyperpolarized [1-13C]dehydroascorbic acid reduction using 13C magnetic resonance spectroscopy. Timm, K. N., Hu, D-E., Williams, M., Wright, A. J., Kettunen, M. I., Kennedy, B. W. C., Larkin, T. J., Dzien, P., Marco-Rius, I., Bohndiek, S. E., and Brindle, K. M. (2017) J. Biol. Chem. 292, 1737-1748.
Analysis of heterogeneity in T-2-weighted MR images can differentiate pseudoprogression from progression in glioblastoma. Booth, T. C., Larkin, T. J., Yuan, Y., Kettunen, M. I., Dawson, S. N., Scoffings, D., Canuto, H. C., Vowler, S. L., Kirschenlohr, H., Hobson, M. P., Markowetz, F., Jefferies, S., and Brindle, K. M. (2017) Plos One 12, 20
Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I. Neves, A. A., Xie, B. W., Fawcett, S., Alam, I. S., Witney, T. H., de Backer, M. M., Summers, J., Hughes, W., McGuire, S., Soloviev, D., Miller, J., Howat, W. J., Hu, D. E., Rodrigues, T. B., Lewis, D. Y., and Brindle, K. M. (2017) J. Nucl. Med. 58, 881-887.
Optoacoustic detection of early therapy-induced tumor cell death using a targeted imaging agent. Xie, B., Tomaszewski, M. R., Neves, A. A., Ros, S., Hu, D-E., McGuire, S., Mullins, S. R., Tice, D., Sainson, R. C. A., Bohndiek, S. E., Wilkinson, R. W., Brindle, K. M. (2017) Clin. Cancer Res. 23, 6893–6903.
Brain tumor imaging. Brindle, K. M., Izquierdo-Garcia, J. L., Lewis, D. Y., Mair, R. J., and Wright, A. J. (2017) J. Clin. Oncol. 35, 2432 – 2439.
Dynamic 1H imaging of hyperpolarized [1-13C]lactate in vivo using a reverse INEPT experiment. Wang, J., Kreis, F., Wright, A. J., Hesketh, R. L., Levitt, M. H., and Brindle, K. M. (2018) Magn. Reson. Med. 79, 741–747.
A referenceless Nyquist ghost correction workflow for echo planar imaging of hyperpolarized [1-13C]pyruvate and [1-13C]lactate. Wang, J. Z., Wright, A. J., Hesketh, R. L., Hu, D. E., and Brindle, K. M. (2018) NMR Biomed. 31, 13
Detection of early neoplasia in Barrett's esophagus using lectin-based near-infrared imaging: an ex vivo study on human tissue. Neves, A.A., Di Pietro, M., O'Donovan, M., Waterhouse, D.J., Bohndiek, S.E., Brindle, K.M. and Fitzgerald, R.C. (2018) Endoscopy 50, 618-625.
Magnetic resonance imaging of cancer metabolism with hyperpolarized C-13 labeled cell metabolites. Hesketh, R.L. and Brindle, K.M. (2018) Current Opinion in Chemical Biology 45, 187-194.
18F-fluoroethyltyrosine-induced Cerenkov Luminescence Improves Image-Guided Surgical Resection of Glioma. Lewis, D.Y., Mair, R., Wright, A., Allinson, K., Lyons, S.K., Booth, T., Jones, J., Bielik, R., Soloviev, D. and Brindle, K.M. (2018) Theranostics 8, 3991-4002.
Metabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma. Mair, R., Wright, A.J., Ros, S., Hu, D.E., Booth, T., Kreis, F., Rao, J., Watts, C. and Brindle, K.M. (2018) Cancer Research 78, 5408-5418.
Increased hyperpolarized [1-13C]lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C-labelled bicarbonate. Wright, A.J., Husson, Z.M.A., Hu, D.E., Callejo, G., Brindle, K.M. and Smith, E.S. (2018) NMR in Biomedicine 31, e3892.
Hyperpolarized 13C spectroscopic imaging using single-shot 3D sequences with unpaired adiabatic refocusing pulses. Wang, J.Z., Hesketh, R.L., Wright, A.J. and Brindle, K.M. (2018) NMR in Biomedicine 31, e4004.
Sub-minute kinetics of human red cell fumarase: H-1 spin-echo NMR spectroscopy and 13C rapid-dissolution dynamic nuclear polarization. Shishmarev, D., Wright, A.J., Rodrigues, T.B., Pileio, G., Stevanato, G., Brindle, K.M. and Kuchel, P.W. (2018) NMR in Biomedicine 31, e3870.
Analysis of 13C and 14C labeling in pyruvate and lactate in tumor and blood of lymphoma-bearing mice injected with 13C- and 14C-labeled pyruvate. Serrao, E.M., Kettunen, M.I., Rodrigues, T.B., Lewis, D.Y., Gallagher, F.A., Hu, D.E. and Brindle, K.M. (2018) NMR in Biomedicine 31, e3901.
Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients. Mouliere, F., Mair, R., Chandrananda, D., Marass, F., Smith, C.G., Su, J., Morris, J., Watts, C., Brindle, K.M. & Rosenfeld, N. (2018) Embo Molecular Medicine 10, pii: e9323.
Measurement of Plasma Cell-Free Mitochondrial Tumor DNA Improves Detection of Glioblastoma in Patient-Derived Orthotopic Xenograft Models. Mair, R., Mouliere, F., Smith, C.G., Chandrananda, D., Gale, D., Marass, F., Tsui, D.W.Y., Massie, C.E., Wright, A.J., Watts, C., Rosenfeld, N. & Brindle, K.M. (2019) Cancer Research 79, 220-230.
Quantifying normal human brain metabolism using hyperpolarized 1-C-13 pyruvate and magnetic resonance imaging. Grist, J.T., McLean, M.A., Riemer, F., Schulte, R.F., Deen, S.S., Zaccagna, F., Woitek, R., Daniels, C.J., Kaggie, J.D., Matys, T., Patterson, I., Slough, R., Gill, A.B., Chhabra, A., Eichenberger, R., Laurent, M.C., Comment, A., Gillard, J.H., Coles, A.J., Tyler, D.J., Wilkinson, I., Basu, B., Lomas, D.J., Graves, M.J., Brindle, K.M. & Gallagher, F.A. (2019) Neuroimage 189, 171-179.
Emerging Technologies to Image Tissue Metabolism. Ntziachristos, V., Pleitez, M.A., Aime, S. & Brindle, K.M. (2019) Cell Metab 29, 518-538.
Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis. Hesketh, R.L., Wang, J.Z., Wright, A.J., Lewis, D.Y., Denton, A.E., Grenfell, R., Miller, J.L., Bielik, R., Gehrung, M., Fala, M., Ros, S., Xie, B.W., Hu, D.E. & Brindle, K.M. (2019) Cancer Research 79, 3557-3569.
