17 results on '"Slough R."'
Search Results
2. Quantifying normal human brain metabolism using hyperpolarized [1– 13 C]pyruvate and magnetic resonance imaging
- Author
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Grist J. T., McLean M. A., Riemer F., Schulte R. F., Deen S. S., Zaccagna F., Woitek R., Daniels C. J., Kaggie J. D., Matyz 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., Grist J.T., McLean M.A., Riemer F., Schulte R.F., Deen S.S., Zaccagna F., Woitek R., Daniels C.J., Kaggie J.D., Matyz 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., and Gallagher F.A.
- Subjects
Pyruvate ,Hyperpolarized ,Metabolism ,Carbon-13 ,Brain ,MRI - Abstract
Hyperpolarized 13 C Magnetic Resonance Imaging ( 13 C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1– 13 C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13 C images demonstrated 13 C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (k PL ) for exchange of the hyperpolarized 13 C label between [1– 13 C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s −1 and the apparent rate constant (k PB ) for the irreversible flux of [1– 13 C]pyruvate to [ 13 C]bicarbonate was 0.002 ± 0.002 s −1 . Imaging also revealed that [1– 13 C]pyruvate, [1– 13 C]lactate and [ 13 C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1– 13 C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.
- Published
- 2019
3. Imaging intralesional heterogeneity of sodium concentration in multiple sclerosis: Initial evidence from 23 Na-MRI
- Author
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Grist J. T., Riemer F., McLean M. A., Matys T., Zaccagna F., Hilborne S. F., Mason J. P., Patterson I., Slough R., Kaggie J., Deen S. S., Graves M. J., Jones J. L., Coles A. J., Gallagher F. A., Grist J.T., Riemer F., McLean M.A., Matys T., Zaccagna F., Hilborne S.F., Mason J.P., Patterson I., Slough R., Kaggie J., Deen S.S., Graves M.J., Jones J.L., Coles A.J., and Gallagher F.A.
- Subjects
Multiple sclerosis ,3-tesla ,Na ,High-resolution ,Extracellular sodium ,Intracellular sodium - Abstract
Sodium MRI ( 23 Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution 23 Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using 23 Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p < 0.01), as well as a heterogeneous distribution of both the total tissue sodium concentration and the intracellular-weighted sodium concentration.
- Published
- 2018
4. Effect of hyoscine butylbromide on prostate multiparametric MRI anatomical and functional image quality
- Author
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Slough, R. A., Caglic, I., Hansen, N. L., Patterson, A. J., Barrett, T., Slough, R. A., Caglic, I., Hansen, N. L., Patterson, A. J., and Barrett, T.
- Abstract
AIM: To evaluate the effect of the spasmolytic agent hyoscine butylbromide (HBB) on the quality of anatomical and functional imaging of the prostate. MATERIALS AND METHODS: One hundred and seventy-three patients were included in this retrospective study. Eighty-seven patients received intravenous HBB prior to scanning (HBB group) and 86 patients did not (non-HBB group). Multiparametric (mp) 3 T magnetic resonance imaging (MRI) was performed using a 32-channel body coil. Two radiologists independently evaluated the image quality of T2-weighted imaging (WI), diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps, using a five-point Likert scale. DWI was further assessed for distortion and artefact (four-point Likert scale), and T2WI for the presence of motion artefact or blurring. Dynamic contrast-enhanced (DCE) image quality was assessed by recording the number of corrupt contrast curve data points. RESULTS: T2W image quality in the HBB group was significantly higher than in the non-HBB group (3.63 +/- 1.11 versus 2.84 +/- 0.899); p< 0.001. The HBB group also showed significantly less T2W motion and T2W blur than the non-HBB group (23% and 51.7% versus 53.5% and 83.7%, respectively; p< 0.001); however, there was no significant improvement in DWI or ADC image quality, or DWI degree of distortion or artefact. There was a trend towards a lower number of corrupted data points from the contrast curve (2.47 +/- 2.44 versus 3.68 +/- 2.64), but this did not reach significance (p = 0.052). CONCLUSION: Administration of HBB significantly improves the image quality of T2WI images. These results provide evidence for the use of HBB in routine patient preparation prior to prostate mpMRI. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
- Published
- 2018
5. An infant with trisomy 9 mosaicism and features of CHARGE association
- Author
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Walker, M E, primary, Slough, R I, additional, Bove, K E, additional, and Hopkin, R J, additional
- Published
- 2000
- Full Text
- View/download PDF
6. Imaging breast cancer using hyperpolarized carbon-13 MRI
- Author
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Turid Torheim, Martin J. Graves, Surrin S. Deen, Sarah Hilborne, Anita Chhabra, Matthew Locke, Zoya Kingsbury, Fiona J. Gilbert, Chris Boursnell, Ramona Woitek, Mark T. Ross, Heather Biggs, Charlie J. Daniels, Mary A. McLean, Frank Riemer, Elena Provenzano, Oscar M. Rueda, James T. Grist, Andrew J. Patterson, Emma Harrison, Ian B. Wilkinson, Suet-Feung Chin, Amy Frary, Carlos Caldas, Justine Kane, Andrew B. Gill, Jean Abraham, Ferdia A. Gallagher, Joshua D. Kaggie, Titus Lanz, Kevin M. Brindle, Bruno Carmo, Marie-Christine Laurent, Rhys Slough, David J. Lomas, Stephan Ursprung, Evis Sala, Amy Schiller, Raquel Manzano Garcia, Richard D. Baird, Ilse Patterson, James Wason, Fulvio Zaccagna, Bristi Basu, Gallagher, Ferdia A [0000-0003-4784-5230], Woitek, Ramona [0000-0002-9146-9159], Manzano Garcia, Raquel [0000-0002-5124-8992], Chhabra, Anita [0000-0002-9899-8010], Grist, James T [0000-0001-7223-4031], Torheim, Turid [0000-0001-6191-2036], Deen, Surrin S [0000-0002-6206-7337], Apollo - University of Cambridge Repository, Gallagher F.A., Woitek R., McLean M.A., Gill A.B., Garcia R.M., Provenzano E., Riemer F., Kaggie J., Chhabra A., Ursprung S., Grist J.T., Daniels C.J., Zaccagna F., Laurent M.-C., Locke M., Hilborne S., Frary A., Torheim T., Boursnell C., Schiller A., Patterson I., Slough R., Carmo B., Kane J., Biggs H., Harrison E., Deen S.S., Patterson A., Lanz T., Kingsbury Z., Ross M., Basu B., Baird R., Lomas D.J., Sala E., Wason J., Rueda O.M., Chin S.-F., Wilkinson I.B., Graves M.J., Abraham J.E., Gilbert F.J., Caldas C., and Brindle K.M.
- Subjects
Monocarboxylic Acid Transporters ,Medical Sciences ,Lactate dehydrogenase A ,Muscle Proteins ,Breast Neoplasms ,Hyperpolarized carbon-13 MRI ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Pyruvic Acid ,medicine ,Humans ,education ,Metabolic Imaging ,030304 developmental biology ,Cancer Metabolism ,Carbon Isotopes ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,L-Lactate Dehydrogenase ,Symporters ,medicine.diagnostic_test ,Chemistry ,Magnetic resonance spectroscopic imaging ,Magnetic resonance imaging ,Metabolism ,Biological Sciences ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Magnetic Resonance Imaging ,3. Good health ,030220 oncology & carcinogenesis ,Invasive lobular carcinoma ,Cancer research ,Immunohistochemistry ,Female - Abstract
Significance Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group., Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.
- Published
- 2020
7. Ternary vapor--liquid equilibria predicted from the binary system data UF$sub 6$--HF, UF$sub 6$--F114, HF--F114
- Author
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Slough, R
- Published
- 1973
8. Emotion-related Processes Between Parents and Adolescents: Evidence for Bidirectional Effects over Time.
- Author
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Miller-Slough R, Parungao D, West C, and Dunsmore JC
- Subjects
- Humans, Male, Female, Adolescent, Adolescent Behavior psychology, Sex Factors, Adult, Parents psychology, Longitudinal Studies, Parent-Child Relations, Emotions physiology, Socialization
- Abstract
Parent emotion socialization has long been studied in relation to children's socioemotional adjustment. Little attention has been paid to how parents' socialization responses are shaped by youth characteristics over time, such as emotional lability. The present study explored the mutual influence between parent emotion socialization and adolescent emotional lability. Participants were 87 adolescents ( M = 14.23 years old, SD = .50; 50 girls) and their parents, who completed questionnaires at three time points from 8
th grade through 10th grade. Hierarchical linear modeling demonstrated mutual influences between parent emotion socialization and adolescent emotional lability, with relations moderated by adolescent gender. Increases in parents' reward of negative emotion predicted decreased emotional lability in girls. Parents' increased magnification of negative emotions corresponded to decreased emotional lability in boys. Boys' increases in emotional lability predicted decreased parental magnification of negative emotions over time. Increases in parents' magnification of negative emotions predicted increased emotional lability in girls. Girls' increases in emotional lability corresponded to increased parental magnification over time. There were no longitudinal effects of adolescent emotional lability on parents' reward, override, and punishment of negative emotions. Future directions and clinical applications are discussed.- Published
- 2024
- Full Text
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9. Loneliness and Alcohol use among College Students During the COVID-19 Pandemic in Rural Appalachia.
- Author
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Ahuja M, Miller-Slough R, Adebayo-Abikoye E, Williams C, Haubner A, Dooley MG, Bansal M, Sathiyaseelan T, Pons A, Karki A, Al Ksir K, Samuel B, Tchoua P, Schuver T, and Fernandopulle P
- Abstract
Objective: Binge drinking and heavy alcohol use are highly prevalent among college students. During the COVID-19 pandemic, due to lockdown restrictions and other challenges, many college students were burdened with loneliness, which can contribute to chronic stress, and substance use. The current study explores the association between loneliness and various levels of alcohol use among college students in the rural, underserved region of Central Appalachia, USA., Methods: Data were collected from a regional sample (n = 320) of college age adults, age 18-25 in the Central Appalachian region. The UCLA-3 item Loneliness Scale (UCLA-3) was used in the study to evaluate loneliness. Logistic regression analysis was conducted to assess the association between levels of loneliness and three separate outcomes, including past year binge drinking, past year heavy alcohol use, and past year weekly alcohol use., Results: Overall, 25.5% of the participants reported severe loneliness, 33.6% reported moderate, and 40.9% reported low levels of loneliness. Results of the adjusted models revealed that severe loneliness was associated with higher odds of heavy alcohol use (AOR = 1.89, 95% CI [1.02, 3.50]) and binge drinking (AOR = 2.96, 95% CI [1.16, 7.51]), and not associated with weekly alcohol use., Conclusion: The study found that higher levels of loneliness were linked to both binged drinking and heavy alcohol use. Further efforts for counseling and treatment among college students who are burdened with severe loneliness should be considered. The chronic stress associated with severe loneliness needs to be further addressed, particularly among emerging adults., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
- Published
- 2024
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10. Imaging Glioblastoma Metabolism by Using Hyperpolarized [1- 13 C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.
- Author
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Zaccagna F, McLean MA, Grist JT, Kaggie J, Mair R, Riemer F, Woitek R, Gill AB, Deen S, Daniels CJ, Ursprung S, Schulte RF, Allinson K, Chhabra A, Laurent MC, Locke M, Frary A, Hilborne S, Patterson I, Carmo BD, Slough R, Wilkinson I, Basu B, Wason J, Gillard JH, Matys T, Watts C, Price SJ, Santarius T, Graves MJ, Jefferies S, Brindle KM, and Gallagher FA
- Subjects
- Bicarbonates, Humans, Lactate Dehydrogenase 5, Lactic Acid, Male, Middle Aged, Prospective Studies, Pyruvic Acid metabolism, Glioblastoma diagnostic imaging
- Abstract
Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (
13 C) MRI to monitor the exchange of the hyperpolarized13 C label between injected [1-13 C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned13 C-hydrogen 1 head coil. Hyperpolarized [1-13 C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP ( P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP ( P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers ( P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized13 C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized13 C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.- Published
- 2022
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11. Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.
- Author
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Woitek R, McLean MA, Ursprung S, Rueda OM, Manzano Garcia R, Locke MJ, Beer L, Baxter G, Rundo L, Provenzano E, Kaggie J, Patterson A, Frary A, Field-Rayner J, Papalouka V, Kane J, Benjamin AJV, Gill AB, Priest AN, Lewis DY, Russell R, Grimmer A, White B, Latimer-Bowman B, Patterson I, Schiller A, Carmo B, Slough R, Lanz T, Wason J, Schulte RF, Chin SF, Graves MJ, Gilbert FJ, Abraham JE, Caldas C, Brindle KM, Sala E, and Gallagher FA
- Subjects
- Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Female, Follow-Up Studies, Humans, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local metabolism, Prognosis, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology, Carbon Isotopes analysis, Magnetic Resonance Imaging methods, Neoadjuvant Therapy methods, Neoplasm Recurrence, Local pathology
- Abstract
Hyperpolarized
13 C-MRI is an emerging tool for probing tissue metabolism by measuring13 C-label exchange between intravenously injected hyperpolarized [1-13 C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized13 C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric1 H-MRI and hyperpolarized13 C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A ( LDHA ), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized13 C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques., (©2021 The Authors; Published by the American Association for Cancer Research.)- Published
- 2021
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12. Hyperpolarized 13 C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.
- Author
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Woitek R, McLean MA, Gill AB, Grist JT, Provenzano E, Patterson AJ, Ursprung S, Torheim T, Zaccagna F, Locke M, Laurent MC, Hilborne S, Frary A, Beer L, Rundo L, Patterson I, Slough R, Kane J, Biggs H, Harrison E, Lanz T, Basu B, Baird R, Sala E, Graves MJ, Gilbert FJ, Abraham JE, Caldas C, Brindle KM, and Gallagher FA
- Subjects
- Contrast Media, Female, Humans, Magnetic Resonance Imaging, Middle Aged, Prospective Studies, Treatment Outcome, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Neoadjuvant Therapy
- Abstract
Purpose: To compare hyperpolarized carbon 13 (
13 C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer., Materials and Methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent13 C MRI after injection of hyperpolarized [1-carbon 13 {13 C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The13 C-labeled lactate-to-pyruvate ratio derived from hyperpolarized13 C MRI and the pharmacokinetic parameters transfer constant ( Ktrans ) and washout parameter ( kep ) derived from DCE MRI were compared before and after treatment., Results: Exchange of the13 C label between injected hyperpolarized [1-13 C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the13 C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment., Conclusion: Hyperpolarized13 C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license., (2020 by the Radiological Society of North America, Inc.)- Published
- 2020
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13. Imaging breast cancer using hyperpolarized carbon-13 MRI.
- Author
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Gallagher FA, Woitek R, McLean MA, Gill AB, Manzano Garcia R, Provenzano E, Riemer F, Kaggie J, Chhabra A, Ursprung S, Grist JT, Daniels CJ, Zaccagna F, Laurent MC, Locke M, Hilborne S, Frary A, Torheim T, Boursnell C, Schiller A, Patterson I, Slough R, Carmo B, Kane J, Biggs H, Harrison E, Deen SS, Patterson A, Lanz T, Kingsbury Z, Ross M, Basu B, Baird R, Lomas DJ, Sala E, Wason J, Rueda OM, Chin SF, Wilkinson IB, Graves MJ, Abraham JE, Gilbert FJ, Caldas C, and Brindle KM
- Subjects
- Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Carbon Isotopes chemistry, Carbon Isotopes metabolism, Female, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, L-Lactate Dehydrogenase genetics, L-Lactate Dehydrogenase metabolism, Magnetic Resonance Imaging instrumentation, Monocarboxylic Acid Transporters genetics, Monocarboxylic Acid Transporters metabolism, Muscle Proteins genetics, Muscle Proteins metabolism, Pyruvic Acid chemistry, Pyruvic Acid metabolism, Symporters genetics, Symporters metabolism, Breast Neoplasms diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using
13 C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized13 C label exchange between injected [1-13 C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic13 C MRSI was performed following injection of hyperpolarized [1-13 C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes13 C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized13 C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume ( R = 0.903, P = 0.005) and MCT 1 ( R = 0.85, P = 0.032) and HIF1α expression ( R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13 C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia., Competing Interests: Competing interest statement: A research agreement is in place between GE Healthcare and K.M.B. and F.A.G., (Copyright © 2020 the Author(s). Published by PNAS.)- Published
- 2020
- Full Text
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14. Longitudinal Patterns in Parent and Friend Emotion Socialization: Associations With Adolescent Emotion Regulation.
- Author
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Miller-Slough R and Dunsmore JC
- Subjects
- Adolescent, Educational Status, Female, Humans, Longitudinal Studies, Male, Parent-Child Relations, Social Behavior, Socialization, Adolescent Behavior psychology, Adolescent Development physiology, Emotional Regulation physiology, Friends psychology, Parents psychology
- Abstract
Adolescents learn about emotions through interacting with parents and friends, though there is limited longitudinal research on this topic. This study examined longitudinal patterns in parent and friend emotion socialization and adolescent emotion regulation. Eighty-seven adolescents reported on parent and friend emotion socialization. Parents reported on adolescent emotion regulation. Parents' responses were stable over time and across gender. Friends of girls reciprocated negative emotions more and were less punitive over time, whereas friends of boys increased in comforting and decreased in neglect of negative emotions. Parents and friends evidenced unique effects on adolescent emotion regulation, and the effect of friend socialization responses differed for girls and boys. Future research should examine combinatory influences of multiple socializers on adolescent adjustment., (© 2018 Society for Research on Adolescence.)
- Published
- 2019
- Full Text
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15. Quantifying normal human brain metabolism using hyperpolarized [1- 13 C]pyruvate and magnetic resonance imaging.
- Author
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Grist JT, McLean MA, Riemer F, Schulte RF, Deen SS, Zaccagna F, Woitek R, Daniels CJ, Kaggie JD, Matys T, Patterson I, Slough R, Gill AB, Chhabra A, Eichenberger R, Laurent MC, Comment A, Gillard JH, Coles AJ, Tyler DJ, Wilkinson I, Basu B, Lomas DJ, Graves MJ, Brindle KM, and Gallagher FA
- Subjects
- Adult, Female, Humans, Male, Brain diagnostic imaging, Brain metabolism, Carbon Isotopes, Magnetic Resonance Imaging methods, Neuroimaging methods, Pyruvic Acid
- Abstract
Hyperpolarized
13 C Magnetic Resonance Imaging (13 C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1-13 C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of13 C images demonstrated13 C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (kPL ) for exchange of the hyperpolarized13 C label between [1-13 C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s-1 and the apparent rate constant (kPB ) for the irreversible flux of [1-13 C]pyruvate to [13 C]bicarbonate was 0.002 ± 0.002 s-1 . Imaging also revealed that [1-13 C]pyruvate, [1-13 C]lactate and [13 C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-13 C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
16. Imaging intralesional heterogeneity of sodium concentration in multiple sclerosis: Initial evidence from 23 Na-MRI.
- Author
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Grist JT, Riemer F, McLean MA, Matys T, Zaccagna F, Hilborne SF, Mason JP, Patterson I, Slough R, Kaggie J, Deen SS, Graves MJ, Jones JL, Coles AJ, and Gallagher FA
- Subjects
- Adult, Analysis of Variance, Brain drug effects, Disability Evaluation, Female, Humans, Imaging, Three-Dimensional, Sodium Radioisotopes pharmacokinetics, Brain diagnostic imaging, Magnetic Resonance Imaging, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis metabolism, Sodium metabolism
- Abstract
Sodium MRI (
23 Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution23 Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using23 Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p<0.01), as well as a heterogeneous distribution of both the total tissue sodium concentration and the intracellular-weighted sodium concentration., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
17. Effect of hyoscine butylbromide on prostate multiparametric MRI anatomical and functional image quality.
- Author
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Slough RA, Caglic I, Hansen NL, Patterson AJ, and Barrett T
- Subjects
- Adult, Aged, Artifacts, Contrast Media, Humans, Image Enhancement methods, Male, Middle Aged, Organometallic Compounds, Prostate anatomy & histology, Prostate drug effects, Retrospective Studies, Butylscopolammonium Bromide pharmacology, Magnetic Resonance Imaging methods, Muscarinic Antagonists pharmacology, Prostate diagnostic imaging
- Abstract
Aim: To evaluate the effect of the spasmolytic agent hyoscine butylbromide (HBB) on the quality of anatomical and functional imaging of the prostate., Materials and Methods: One hundred and seventy-three patients were included in this retrospective study. Eighty-seven patients received intravenous HBB prior to scanning (HBB group) and 86 patients did not (non-HBB group). Multiparametric (mp) 3 T magnetic resonance imaging (MRI) was performed using a 32-channel body coil. Two radiologists independently evaluated the image quality of T2-weighted imaging (WI), diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps, using a five-point Likert scale. DWI was further assessed for distortion and artefact (four-point Likert scale), and T2WI for the presence of motion artefact or blurring. Dynamic contrast-enhanced (DCE) image quality was assessed by recording the number of corrupt contrast curve data points., Results: T2W image quality in the HBB group was significantly higher than in the non-HBB group (3.63±1.11 versus 2.84±0.899); p<0.001. The HBB group also showed significantly less T2W motion and T2W blur than the non-HBB group (23% and 51.7% versus 53.5% and 83.7%, respectively; p<0.001); however, there was no significant improvement in DWI or ADC image quality, or DWI degree of distortion or artefact. There was a trend towards a lower number of corrupted data points from the contrast curve (2.47±2.44 versus 3.68±2.64), but this did not reach significance (p=0.052)., Conclusion: Administration of HBB significantly improves the image quality of T2WI images. These results provide evidence for the use of HBB in routine patient preparation prior to prostate mpMRI., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
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