|
1
|
Shang Y, Simegn GL, Gillen K, Yang HJ, Han H. Advancements in MR hardware systems and magnetic field control: B 0 shimming, RF coils, and gradient techniques for enhancing magnetic resonance imaging and spectroscopy. PSYCHORADIOLOGY 2024; 4:kkae013. [PMID: 39258223 PMCID: PMC11384915 DOI: 10.1093/psyrad/kkae013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 07/02/2024] [Accepted: 08/12/2024] [Indexed: 09/12/2024]
Abstract
High magnetic field homogeneity is critical for magnetic resonance imaging (MRI), functional MRI, and magnetic resonance spectroscopy (MRS) applications. B0 inhomogeneity during MR scans is a long-standing problem resulting from magnet imperfections and site conditions, with the main issue being the inhomogeneity across the human body caused by differences in magnetic susceptibilities between tissues, resulting in signal loss, image distortion, and poor spectral resolution. Through a combination of passive and active shim techniques, as well as technological advances employing multi-coil techniques, optimal coil design, motion tracking, and real-time modifications, improved field homogeneity and image quality have been achieved in MRI/MRS. The integration of RF and shim coils brings a high shim efficiency due to the proximity of participants. This technique will potentially be applied to high-density RF coils with a high-density shim array for improved B0 homogeneity. Simultaneous shimming and image encoding can be achieved using multi-coil array, which also enables the development of novel encoding methods using advanced magnetic field control. Field monitoring enables the capture and real-time compensation for dynamic field perturbance beyond the static background inhomogeneity. These advancements have the potential to better use the scanner performance to enhance diagnostic capabilities and broaden applications of MRI/MRS in a variety of clinical and research settings. The purpose of this paper is to provide an overview of the latest advances in B0 magnetic field shimming and magnetic field control techniques as well as MR hardware, and to emphasize their significance and potential impact on improving the data quality of MRI/MRS.
Collapse
Affiliation(s)
- Yun Shang
- Department of Radiology, Weill Medical College of Cornell University, New York, NY 10065, United States
| | - Gizeaddis Lamesgin Simegn
- Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
- F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, United States
| | - Kelly Gillen
- Department of Radiology, Weill Medical College of Cornell University, New York, NY 10065, United States
| | - Hsin-Jung Yang
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA 90048, United States
| | - Hui Han
- Department of Radiology, Weill Medical College of Cornell University, New York, NY 10065, United States
| |
Collapse
|
|
2
|
Marinkovic K, White DR, Alderson Myers A, Parker KS, Arienzo D, Mason GF. Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome. Brain Sci 2023; 13:1666. [PMID: 38137114 PMCID: PMC10741691 DOI: 10.3390/brainsci13121666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 11/28/2023] [Accepted: 11/28/2023] [Indexed: 12/24/2023] Open
Abstract
After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed "long COVID". Their quality of life is adversely impacted by persistent cognitive dysfunction and affective distress, but the underlying neural mechanisms are poorly understood. The present study recruited a group of mostly young, previously healthy adults (24.4 ± 5.2 years of age) who experienced PASC for almost 6 months following a mild acute COVID-19 illness. Confirming prior evidence, they reported noticeable memory and attention deficits, brain fog, depression/anxiety, fatigue, and other symptoms potentially suggestive of excitation/inhibition imbalance. Proton magnetic resonance spectroscopy (1H-MRS) was used to examine the neurochemical aspects of cell signaling with an emphasis on GABA levels in the occipital cortex. The PASC participants were compared to a control (CNT) group matched in demographics, intelligence, and an array of other variables. Controlling for tissue composition, biological sex, and alcohol intake, the PASC group had lower GABA+/water than CNT, which correlated with depression and poor sleep quality. The mediation analysis revealed that the impact of PASC on depression was partly mediated by lower GABA+/water, indicative of cortical hyperexcitability as an underlying mechanism. In addition, N-acetylaspartate (NAA) tended to be lower in the PASC group, possibly suggesting compromised neuronal integrity. Persistent neuroinflammation may contribute to the pathogenesis of PASC-related neurocognitive dysfunction.
Collapse
Affiliation(s)
- Ksenija Marinkovic
- Spatio-Temporal Brain Imaging Lab, Department of Psychology, San Diego State University, San Diego, CA 92182, USA (A.A.M.); (D.A.)
- Department of Radiology, University of California, San Diego, CA 92093, USA
| | - David R. White
- Spatio-Temporal Brain Imaging Lab, Department of Psychology, San Diego State University, San Diego, CA 92182, USA (A.A.M.); (D.A.)
| | - Austin Alderson Myers
- Spatio-Temporal Brain Imaging Lab, Department of Psychology, San Diego State University, San Diego, CA 92182, USA (A.A.M.); (D.A.)
- Department of Psychiatry, University of California, San Diego, CA 92093, USA
| | - Katie S. Parker
- Spatio-Temporal Brain Imaging Lab, Department of Psychology, San Diego State University, San Diego, CA 92182, USA (A.A.M.); (D.A.)
| | - Donatello Arienzo
- Spatio-Temporal Brain Imaging Lab, Department of Psychology, San Diego State University, San Diego, CA 92182, USA (A.A.M.); (D.A.)
- Department of Radiology, University of California, San Diego, CA 92093, USA
| | - Graeme F. Mason
- Department of Radiology and Biomedical Imaging, Psychiatry, and Biomedical Engineering, Yale University, New Haven, CT 06520, USA;
| |
Collapse
|
|
3
|
Pomp L, Jeneson JAL, van der Pol WL, Bartels B. Electrophysiological and Imaging Biomarkers to Evaluate Exercise Training in Patients with Neuromuscular Disease: A Systematic Review. J Clin Med 2023; 12:6834. [PMID: 37959299 PMCID: PMC10647337 DOI: 10.3390/jcm12216834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/13/2023] [Accepted: 10/18/2023] [Indexed: 11/15/2023] Open
Abstract
Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, the objective of this systematic review was to critically appraise and summarize the current evidence for the sensitivity of quantitative, non-invasive biomarkers, based on imaging and electrophysiological techniques, for measuring the effects of physical exercise training. We identified a wide variety of biomarkers, including imaging techniques, i.e., magnetic resonance imaging (MRI) and ultrasound, surface electromyography (sEMG), magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS). Imaging biomarkers, such as muscle maximum area and muscle thickness, and EMG biomarkers, such as compound muscle action potential (CMAP) amplitude, detected significant changes in muscle morphology and neural adaptations following resistance training. MRS and NIRS biomarkers, such as initial phosphocreatine recovery rate (V), mitochondrial capacity (Qmax), adenosine phosphate recovery half-time (ADP t1/2), and micromolar changes in deoxygenated hemoglobin and myoglobin concentrations (Δ[deoxy(Hb + Mb)]), detected significant adaptations in oxidative metabolism after endurance training. We also identified biomarkers whose clinical relevance has not yet been assessed due to lack of sufficient study.
Collapse
Affiliation(s)
- Lisa Pomp
- Child Development and Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Jeroen Antonius Lodewijk Jeneson
- Child Development and Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - W. Ludo van der Pol
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Bart Bartels
- Child Development and Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| |
Collapse
|
|
4
|
Häussinger D, Dhiman RK, Felipo V, Görg B, Jalan R, Kircheis G, Merli M, Montagnese S, Romero-Gomez M, Schnitzler A, Taylor-Robinson SD, Vilstrup H. Hepatic encephalopathy. Nat Rev Dis Primers 2022; 8:43. [PMID: 35739133 DOI: 10.1038/s41572-022-00366-6] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/12/2022] [Indexed: 01/18/2023]
Abstract
Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging.
Collapse
Affiliation(s)
- Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Radha K Dhiman
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (Uttar Pradesh), India
| | - Vicente Felipo
- Laboratory of Neurobiology, Centro de Investigación Principe Felipe, Valencia, Spain
| | - Boris Görg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Rajiv Jalan
- Liver Failure Group ILDH, Division of Medicine, UCL Medical School, Royal Free Campus, London, UK.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Gerald Kircheis
- Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg an der Havel, Brandenburg Medical School, Brandenburg an der Havel, Germany
| | - Manuela Merli
- Department of Translational and Precision Medicine, Universita' degli Studi di Roma - Sapienza, Roma, Italy
| | | | - Manuel Romero-Gomez
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, UK
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
5
|
Marinkovic K, Alderson Myers AB, Arienzo D, Sereno MI, Mason GF. Cortical GABA levels are reduced in young adult binge drinkers: Association with recent alcohol consumption and sex. Neuroimage Clin 2022; 35:103091. [PMID: 35753236 PMCID: PMC9240858 DOI: 10.1016/j.nicl.2022.103091] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 06/10/2022] [Accepted: 06/18/2022] [Indexed: 01/12/2023]
Abstract
Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication depresses neural activity via complex signaling mechanisms by enhancing inhibition mediated by gamma-amino butyric acid (GABA), and by decreasing excitatory glutamatergic effects. Evidence primarily rooted in animal research indicates that the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. However, human evidence on the compensatory reduction in GABA signaling is scant. The neurochemical aspect of this mechanistic model was evaluated in the present study with proton magnetic resonance spectroscopy (1H-MRS) which is sensitive to GABA plus macromolecule signal (GABA + ). Furthermore, we examined sex differences in GABA + levels as a function of a recent history of binge drinking, given interactions between endogenous neurosteroids, GABA signaling, and alcohol. The study recruited young adult women and men (22.2 ± 2.8 years of age) who were classified as binge drinkers (BDs, N = 52) if they reported ≥ 5 binge episodes in the previous six months. Light drinkers (LDs, N = 49) reported drinking regularly, but not exceeding ≤ 2 binge episodes in the past six months. GABA-edited 1H-MR spectra were acquired from the occipital cortex at 3 T with the MEGA-PRESS sequence. GABA + signal was analyzed relative to water and total creatine (Cr) levels as a function of binge drinking history and sex. Controlling for within-voxel tissue composition, both GABA + indices showed decreased GABA + levels in BDs relative to LDs. The reduced GABA + concentration was associated with occasional high-intensity drinking in the BD group. This evidence is consistent with compensatory GABA downregulation that accompanies alcohol misuse, tipping the excitation/inhibition balance towards hyperexcitability. Analysis of the time course of GABA + neuroplasticity indicated that GABA + was lowest when measured one day after the last drinking occasion in BDs. While the BD vs LD differences were primarily driven by LD women, there was no interaction between Sex and a history of binge drinking. GABA + was higher in LD women compared to LD men. Aligned with the allostasis model, the mechanistic compensatory GABA downregulation observed in young emerging adults engaging in occasional binge drinking complements direct neural measures of hyperexcitability in BDs. Notably, these results suggest that neuroadaptation to alcohol is detectable at the levels of consumption that are within a normative range, and may contribute to adverse health outcomes.
Collapse
Affiliation(s)
- Ksenija Marinkovic
- Department of Psychology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA; Department of Radiology, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
| | - Austin B Alderson Myers
- Department of Psychology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA.
| | - Donatello Arienzo
- Department of Psychology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA
| | - Martin I Sereno
- Department of Psychology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA.
| | - Graeme F Mason
- Department of Radiology and Biomedical Imaging, Department of Psychiatry, Department of Biomedical Engineering, Yale University, N-141 TAC-MRRC, 300 Cedar Street, New Haven, CT 06520, USA.
| |
Collapse
|
|
6
|
Xiong XF, Chen DD, Zhu HJ, Ge WH. Prognostic value of endogenous and exogenous metabolites in liver transplantation. Biomark Med 2020; 14:1165-1181. [PMID: 32969246 DOI: 10.2217/bmm-2020-0073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation has been widely accepted as an effective intervention for end-stage liver diseases and early hepatocellular carcinomas. However, a variety of postoperative complications and adverse reactions have baffled medical staff and patients. Currently, transplantation monitoring relies primarily on nonspecific biochemical tests, whereas diagnosis of multiple complications depends on invasive pathological examination. Therefore, a noninvasive monitoring method with high selectivity and specificity is desperately needed. This review summarized the potential of endogenous small-molecule metabolites as biomarkers for assessing graft function, ischemia-reperfusion injury and liver rejection. Exogenous metabolites, mainly those immunosuppressive agents with high intra- and inter-individual variability, were also discussed for transplantation monitoring.
Collapse
Affiliation(s)
- Xiao-Fu Xiong
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China.,College of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China
| | - Ding-Ding Chen
- College of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China
| | - Huai-Jun Zhu
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China.,Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Wei-Hong Ge
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China
| |
Collapse
|
|
7
|
Cicero L, Cirincione R, Comelli A, Coronnello C, Cassata G. Residue analysis of a synthetic glucocorticoid in liver samples by a 1HMR spectroscopy approach: An exploratory study on animal model. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2020; 37:1640-1650. [PMID: 32726569 DOI: 10.1080/19440049.2020.1787528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Betamethasone is a glucocorticoid authorised in cattle for the treatment of metabolic and inflammatory diseases, but, in Europe, it is illegally employed to improve productive performances. LC-MS/MS is the official control method of veterinary drugs residues in food of animal origin. An experimental study was developed to evaluate the feasibility of proton magnetic resonance spectroscopy (1H-MRS) as a potential alternative approach to detect the presence of betamethasone residues. Eight rat liver samples were collected 24 h post-betamethasone-treatment from experimental and control animals and were analysed by 1H-MRS using a 7-Tesla MRI scanner. 1H-MR reference spectra both of the Bentelan formulation used for treatment, and of three solutions of betamethasone in dimethyl sulphoxide (DMSO) at 5, 10 and 100 mM, respectively, were acquired to fit analyte-peaks in the liver samples spectra. Betamethasone-peaks were found only in the 100 mM betamethasone in DMSO solution spectrum. Betamethasone residues were not detected in any of the tissue samples analysed, probably related to the low concentration of injected drug. These findings allow us to establish, for the first time in the literature, the detection limit (in the range 10-100 mM) of betamethasone for the 7-Tesla MRI scanner used here. Given this very-low sensitivity, we conclude that the evaluated 1H-MR spectroscopy approach is not suitable for the detection of betamethasone residues in edible tissues, since the maximum residue limit imposed by Commission Regulation (EC) 37/2010 for betamethasone in the liver, and metabolic concentrations required to be detected in animal samples from livestock, are far below the detection limit we found.
Collapse
Affiliation(s)
- Luca Cicero
- Istituto Zooprofilattico Sperimentale Della Sicilia "A. Mirri" , Palermo, Italy
| | - Roberta Cirincione
- Istituto Zooprofilattico Sperimentale Della Sicilia "A. Mirri" , Palermo, Italy
| | | | | | - Giovanni Cassata
- Istituto Zooprofilattico Sperimentale Della Sicilia "A. Mirri" , Palermo, Italy
| |
Collapse
|
|
8
|
Valkovič L, Chmelík M, Krššák M. In-vivo 31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism. Anal Biochem 2017; 529:193-215. [PMID: 28119063 PMCID: PMC5478074 DOI: 10.1016/j.ab.2017.01.018] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 01/13/2017] [Accepted: 01/19/2017] [Indexed: 01/18/2023]
Abstract
In addition to direct assessment of high energy phosphorus containing metabolite content within tissues, phosphorus magnetic resonance spectroscopy (31P-MRS) provides options to measure phospholipid metabolites and cellular pH, as well as the kinetics of chemical reactions of energy metabolism in vivo. Even though the great potential of 31P-MR was recognized over 30 years ago, modern MR systems, as well as new, dedicated hardware and measurement techniques provide further opportunities for research of human biochemistry. This paper presents a methodological overview of the 31P-MR techniques that can be used for basic, physiological, or clinical research of human skeletal muscle and liver in vivo. Practical issues of 31P-MRS experiments and examples of potential applications are also provided. As signal localization is essential for liver 31P-MRS and is important for dynamic muscle examinations as well, typical localization strategies for 31P-MR are also described.
Collapse
Affiliation(s)
- Ladislav Valkovič
- High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, Oxford, United Kingdom; Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia.
| | - Marek Chmelík
- High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria; Institute for Clinical Molecular MRI in Musculoskeletal System, Karl Landsteiner Society, Vienna, Austria
| | - Martin Krššák
- High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria; Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
9
|
Bulakbasi N, Kocaoglu M, Sanal H, Tayfun C. Efficacy of in vivo31Phosphorus Magnetic Resonance Spectroscopy in Differentiation and Staging of Adult Human Brain Tumors. Neuroradiol J 2016; 20:646-55. [DOI: 10.1177/197140090702000608] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2007] [Accepted: 07/09/2007] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to evaluate the efficacy of 31P magnetic resonance spectroscopy (31P-MRS) in the differentiation and staging of brain tumors. Fifteen volunteers and 44 patients with brain tumors (14 meningiomas, 13 low- and 17 high-grade gliomas) were prospectively evaluated by 31P-MRS. The pH (r=0.493, p<0.001), [Mg+2] (r=0.850, p<0.001) PME/α-ATP (r=0.776, p<0.001), PDE/α-ATP (r=-0.569, p<0.001) and (PCr+β-ATP)/Pi ratios were well correlated with tumor differentiation. High-grade gliomas had significantly higher pH (r=0.912, p<0.001) and [Mg+2] (r=0.855, p<0.001) and PME/α-ATP (r=0.894, p<0.001) ratio, and lower PCr/α-ATP (r= −0.959, p<0.001), Pi/α-ATP (r= −0.788, p<0.001) and PDE/α-ATP ratios (r=−0.968, p<0.001) than those of low-grade gliomas. Changes in 31P-MRS parameters by the degree of malignancy are good indicators of increased anaerobic metabolism and hypoxia of tumoral tissue to compensate intratumoral energy deficiency. 31P-MRS parameters are very useful for grading and differentiation of brain tumors.
Collapse
Affiliation(s)
- N. Bulakbasi
- Radiology Department, Gulhane Military Medical Academy; Ankara, Turkey
| | - M. Kocaoglu
- Radiology Department, Gulhane Military Medical Academy; Ankara, Turkey
| | - H.T. Sanal
- Radiology Department, Gulhane Military Medical Academy; Ankara, Turkey
| | - C. Tayfun
- Radiology Department, Gulhane Military Medical Academy; Ankara, Turkey
| |
Collapse
|
|
10
|
Bonneau E, Tétreault N, Robitaille R, Boucher A, De Guire V. Metabolomics: Perspectives on potential biomarkers in organ transplantation and immunosuppressant toxicity. Clin Biochem 2016; 49:377-84. [DOI: 10.1016/j.clinbiochem.2016.01.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 12/23/2015] [Accepted: 01/07/2016] [Indexed: 12/27/2022]
|
|
11
|
Tognarelli JM, Dawood M, Shariff MI, Grover VP, Crossey MM, Cox IJ, Taylor-Robinson SD, McPhail MJ. Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians. J Clin Exp Hepatol 2015; 5:320-8. [PMID: 26900274 PMCID: PMC4723643 DOI: 10.1016/j.jceh.2015.10.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 10/26/2015] [Indexed: 12/12/2022] Open
Abstract
Magnetic resonance spectroscopy (MRS) provides a non-invasive 'window' on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11-14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information. We discuss the background physics the busy clinician needs to know before considering using the technique as an investigative tool. Some potential applications of hepatic and cerebral MRS in chronic liver disease are also discussed.
Collapse
Key Words
- CPMG, Carr-Purcell-Meiboom-Gill sequence
- CSI, chemical shift imaging
- FID, free induction decay
- K, Kelvin
- KEGG, Kyoto Encyclopedia for Genes and Genomes
- MR, magnetic resonance
- MRI, magnetic resonance imaging
- MRS, magnetic resonance spectroscopy
- MSEA, metabolite set enrichment analysis
- NMR, nuclear magnetic resonance
- NOESY, nuclear Overhauser enhancement spectroscopy
- PC, principal components
- PCA, principal components analysis
- PLS-DA, partial least squared discriminant analysis
- PRESS, point-resolved spectroscopy
- STEAM, stimulated echo acquisition mode
- T, Tesla
- T1, spin-lattice relaxation
- T2, spin-spin relaxation
- TE, echo time
- TMAO, trimethylamine N-oxide
- TR, repetition time
- magnetic resonance imaging
- magnetic resonance spectroscopy
- metabolomics
- nuclear magnetic resonance
Collapse
Affiliation(s)
- Joshua M. Tognarelli
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
- Address for correspondence: Joshua Tognarelli, Liver Unit, Department of Medicine, 10th Floor QEQM Wing, St Mary's Hospital, Imperial College London, Praed Street, London W2 1NY, United Kingdom. Tel.: +44 207 886 6454; fax: +44 207 402 2796.Liver Unit, Department of Medicine, 10th Floor QEQM Wing, St Mary's Hospital, Imperial College LondonPraed StreetLondonW2 1NYUnited Kingdom
| | - Mahvish Dawood
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
| | - Mohamed I.F. Shariff
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
| | - Vijay P.B. Grover
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
| | - Mary M.E. Crossey
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
| | - I. Jane Cox
- The Foundation for Liver Research, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom
| | - Simon D. Taylor-Robinson
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
| | - Mark J.W. McPhail
- Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom
| |
Collapse
|
|
12
|
Melo HJDFE, Goldman SM, Szejnfeld J, Faria JF, Huayllas MKP, Andreoni C, Kater CE. Application of a protocol for magnetic resonance spectroscopy of adrenal glands: an experiment with over 100 cases. Radiol Bras 2015; 47:333-41. [PMID: 25741115 PMCID: PMC4341383 DOI: 10.1590/0100-3984.2013.1812] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2013] [Accepted: 04/22/2014] [Indexed: 11/29/2022] Open
Abstract
Objective To evaluate a protocol for two-dimensional (2D) hydrogen proton (1H) magnetic
resonance spectroscopy (MRS) (Siemens Medical Systems; Erlangen, Germany) in the
detection of adrenal nodules and differentiation between benign and malignant
masses (adenomas, pheochromocytomas, carcinomas and metastases). Materials and Methods A total of 118 patients (36 men; 82 women) (mean age: 57.3 ± 13.3 years)
presenting with 138 adrenal nodules/masses were prospectively assessed. A
multivoxel system was utilized with a 2D point-resolved spectroscopy/chemical
shift imaging sequence. The following ratios were calculated: choline
(Cho)/creatine (Cr), 4.0–4.3/Cr, lipid (Lip)/Cr, Cho/Lip and lactate (Lac)/Cr. Results 2D-1H-MRS was successful in 123 (89.13%) lesions. Sensitivity and specificity
values observed for the ratios and cutoff points were the following: Cho/Cr ≥ 1.2,
100% sensitivity, 98.2% specificity (differences between
adenomas/pheochromocytomas and carcinomas/ metastases); 4.0–4.3 ppm/Cr ≥ 1.5,
92.3% sensitivity, 96.9% specificity (differences between
carcinomas/pheochromocytomas and adenomas/metastases); Lac/Cr ≤ –7.449, 90.9%
sensitivity and 77.8% specificity (differences between pheochromocytomas and
carcinomas/adenomas). Conclusion Information provided by 2D-1H-MRS were effective and allowed for the
differentiation between adrenal masses and nodules in most cases of lesions with
> 1.0 cm in diameter.
Collapse
Affiliation(s)
- Homero José de Farias E Melo
- PhD, Assistant Professor, Centro Universitário São Camilo, Collaborator, Department of Imaging Diagnosis - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Suzan M Goldman
- Private Docent, Affiliate Professor, Department of Imaging Diagnosis - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Jacob Szejnfeld
- Private Docent, Associate Professor, Department of Imaging Diagnosis - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Juliano F Faria
- PhD, MD, Radiologist, Sociedade Paulista para o Desenvolvimento da Medicina - Hospital São Paulo (SPDM-HSP), São Paulo, SP, Brazil
| | - Martha K P Huayllas
- Master, MD, Endocrinologist, Department of Endoclinology - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Cássio Andreoni
- Private Docent, Associate Professor, Department of Urology - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Cláudio E Kater
- Postdoc, Associate Professor, Department of Endocrinology - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| |
Collapse
|
|
13
|
Sohlberg S, Wikström AK, Olovsson M, Lindgren P, Axelsson O, Mulic-Lutvica A, Weis J, Wikström J. In vivo ³¹P-MR spectroscopy in normal pregnancy, early and late preeclampsia: a study of placental metabolism. Placenta 2014; 35:318-23. [PMID: 24612844 DOI: 10.1016/j.placenta.2014.02.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Revised: 02/07/2014] [Accepted: 02/11/2014] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Preeclampsia affects about 3% of pregnancies and the placenta is believed to play a major role in its pathophysiology. Lately, the role of the placenta has been hypothesised to be more pronounced in preeclampsia of early (<34 weeks) rather than late (≥ 34 weeks) onset. (31)P Magnetic Resonance Spectroscopy (MRS) enables non-invasive, in vivo studies of placental metabolism. Our aim was to study placental energy and membrane metabolism in women with normal pregnancies and those with early and late onset preeclampsia. METHODS The study population included fourteen women with preeclampsia (five with early onset and nine with late onset preeclampsia) and sixteen women with normal pregnancy (seven with early and nine with late pregnancy). All women underwent a (31)P-MRS examination of the placenta. RESULTS The phosphodiester (PDE) spectral intensity fraction of the total (31)P signal and the phosphodiester/phosphomonoester (PDE/PME) spectral intensity ratio was higher in early onset preeclampsia than in early normal pregnancy (p = 0.03 and p = 0.02). In normal pregnancy the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio increased with increasing gestational age (p = 0.006 and p = 0.001). DISCUSSION Since PDE and PME are related to cell membrane degradation and formation, respectively, our findings indicate increased cell degradation and maybe also decreased cell proliferation in early onset preeclampsia compared to early normal pregnancy, and with increasing gestational age in normal pregnancy. CONCLUSIONS Our findings could be explained by increased apoptosis due to ischaemia in early onset preeclampsia and also increased apoptosis with increasing gestational age in normal pregnancy.
Collapse
Affiliation(s)
- S Sohlberg
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
| | - A-K Wikström
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
| | - M Olovsson
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
| | - P Lindgren
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
| | - O Axelsson
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; The Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
| | - A Mulic-Lutvica
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
| | - J Weis
- Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
| | - J Wikström
- Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
| |
Collapse
|
|
14
|
Fievisohn EM, Sajja VSSS, Vandevord PJ, Hardy WN. Evaluation of impact-induced traumatic brain injury in the Göttingen Minipig using two input modes. TRAFFIC INJURY PREVENTION 2014; 15 Suppl 1:S81-S87. [PMID: 25307402 DOI: 10.1080/15389588.2014.929670] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
OBJECTIVES Two novel injury devices were used to characterize impact-induced traumatic brain injury (TBI). One imparts pure translation, and the other produces combined translation and rotation. The objective of this study was to evaluate the neuropathology associated with two injury devices using proton magnetic resonance spectroscopy (1H-MRS) to quantify metabolic changes and immunohistochemistry (IHC) to evaluate axonal damage in the corpus callosum. METHODS Young adult female Göttingen minipigs were exposed to impact-induced TBI with either the translation-input injury device or the combined-input injury device (n=11/group). Sham animals were treated identically except for the injury event (n=3). The minipigs underwent 1H-MRS scans prior to injury (baseline), approximately 1 h after injury, and 24 h post injury, at which point the brains were extracted for IHC. Metabolites of interest include glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), and γ-aminobutyric acid (GABA). Repeated measures analysis of variance with a least significant difference post hoc test were used to compare the three time points. IHC was performed on paraffin-embedded sections of the corpus callosum with light and heavy neurofilament antibodies. Stained pixel percentages were compared between shams and 24-h survival animals. RESULTS For the translation-input group (27.5-70.1 g), 16 significant metabolite differences were found. Three of these include a significant increase in Gln, both 1 h and 24 h postinjury, and an increase in GABA 24 h after injury. For the combined-input group (40.1-95.9 g; 1,014.5-3,814.9 rad/s2; 7.2-10.8 rad/s), 20 significant metabolite differences were found. Three of these include a significant increase in Glu, an increase in the ratio Glu/Gln, and an increase in the ratio Glu/NAAG 24 h after injury. The IHC analysis revealed significant increases in light and heavy neurofilament for both groups 24 h after injury. CONCLUSIONS Only five metabolite differences were similar between the input modes, most of which are related to inflammation or myelin disruption. The observed metabolite differences indicate important dissimilarities. For the translation-input group, an increase in Gln and GABA suggests a response in the GABA shunt system. For the combined-input group, an increase in Glu, Glu/Gln, and Glu/NAAG suggests glutamate excitotoxicity. Importantly, both of these input modes lead to similar light and heavy neurofilament damage, which indicates axonal disruption. Identifying neuropathological changes that are unique to different injury mechanisms is critical in defining the complexity of TBI and can lead to improved prevention strategies and the development of effective drug therapies.
Collapse
Affiliation(s)
- Elizabeth M Fievisohn
- a Virginia Tech-Wake Forest University, School of Biomedical Engineering and Sciences, Center for Injury Biomechanics, Virginia Polytechnic Institute and State University , Blacksburg , Virginia
| | | | | | | |
Collapse
|
|
15
|
Affiliation(s)
- Alina Adams
- Institut für Technische und Makromolekulare Chemie; RWTH Aachen University; Templergraben 55 52056 Aachen Germany
| | - Bernhard Blümich
- Institut für Technische und Makromolekulare Chemie; RWTH Aachen University; Templergraben 55 52056 Aachen Germany
| |
Collapse
|
|
16
|
Lai TH, Fuh JL, Lirng JF, Lin CP, Wang SJ. Brainstem 1H-MR spectroscopy in episodic and chronic migraine. J Headache Pain 2012; 13:645-51. [PMID: 23070401 PMCID: PMC3484255 DOI: 10.1007/s10194-012-0491-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 10/07/2012] [Indexed: 11/30/2022] Open
Abstract
The pathogenesis of evolution from episodic migraine (EM) to chronic migraine (CM) has not yet been clearly determined. Some studies revealed that dysfunction of the brainstem may play a role. We aimed to determine the brainstem 1H-MR spectroscopic (MRS) findings in episodic and chronic migraine. We recruited patients with EM, CM and controls. Patients with CM were divided into subgroups with and without medication overuse (MO). The 1H-MRS metabolite ratios at the periaqueductal gray (PAG) and bilateral dorsal pons were measured and compared with those in controls. A total of 19 patients with EM, 53 patients with CM (with MO n = 30, without MO n = 23) and 16 control subjects completed the study. Patients with EM had the highest N-acetylaspartate (NAA)/creatine (Cr) ratio at the dorsal pons (right, P = 0.014; left, P = 0.034) in comparison with those of CM and controls. The latter two groups did not differ. Among migraine patients, NAA/Cr ratios at dorsal pons were inversely correlated with headache frequency (right, r = −0.350, P = 0.004; left, r = −0.284, P = 0.019) and intensity (right, r = −0.286, P = 0.019; left, r = −0.244, P = 0.045), but not disease duration. In contrast, the metabolite ratios did not differ at the PAG among the study groups. Of note, MO was not associated with brainstem MRS ratios in patients with CM. The increased NAA/Cr levels may suggest neuronal hypertrophy at the dorsal pons in EM. A progressive dysfunction of this region may occur from EM to CM since the levels declined with increasing headache frequency and intensity.
Collapse
Affiliation(s)
- Tzu-Hsien Lai
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | | | | | | | | |
Collapse
|
|
17
|
Pola A, Sadananthan SA, Yaligar J, Nagarajan V, Han W, Kuchel PW, Velan SS. Skeletal muscle lipid metabolism studied by advanced magnetic resonance spectroscopy. PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 2012; 65:66-76. [PMID: 22781315 DOI: 10.1016/j.pnmrs.2012.02.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Accepted: 02/08/2012] [Indexed: 06/01/2023]
Affiliation(s)
- Arunima Pola
- Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, A*STAR, Singapore
| | | | | | | | | | | | | |
Collapse
|
|
18
|
Winston A, Duncombe C, Li PCK, Gill JM, Kerr SJ, Puls RL, Taylor-Robinson SD, Emery S, Cooper DA. Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy. Neuroradiology 2012; 54:1331-9. [PMID: 22772471 DOI: 10.1007/s00234-012-1061-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2012] [Accepted: 06/20/2012] [Indexed: 10/28/2022]
Abstract
INTRODUCTION Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ((1)H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART. METHODS Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent (1)H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed. RESULTS Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014). CONCLUSIONS Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects.
Collapse
Affiliation(s)
- Alan Winston
- St. Mary's Hospital, Imperial College London, Ground Floor, Clinical Trials, Winston Churchill Wing, Praed Street, London, W2 1NY, UK.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Elemental imaging of MRI contrast agents: benchmarking of LA-ICP-MS to MRI. Anal Bioanal Chem 2012; 403:1641-9. [PMID: 22526651 DOI: 10.1007/s00216-012-5973-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2012] [Revised: 03/20/2012] [Accepted: 03/26/2012] [Indexed: 10/28/2022]
Abstract
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion of Magnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site.
Collapse
|
|
20
|
Abstract
Novel imaging techniques allow the investigation of structural and functional neuropathology of hepatic encephalopathy in greater detail, but limited techniques are applicable to the clinic. Computed tomography and magnetic resonance imaging (MRI) can rule out other diagnoses and, in MRI, give diagnostic features in widely available sequences. An internationally accepted diagnostic framework that includes an objective imaging test to replace or augment psychometry remains elusive. Quantitative MRI is likely to be the best candidate to become this test. The utility of MR and nuclear medical techniques to the clinic and results from recent research are described in this article.
Collapse
Affiliation(s)
- Mark J W McPhail
- Liver and Antiviral Center, Department of Medicine, St Mary's Hospital Campus, Imperial College London, 10th Floor QEQM Wing, South Wharf Street, London W2 1NY, UK.
| | | | | |
Collapse
|
|
21
|
Gender-dependent behavioural impairment and brain metabolites in young adult rats after short term exposure to lead acetate. Toxicol Lett 2012; 210:15-23. [PMID: 22285975 DOI: 10.1016/j.toxlet.2012.01.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 01/12/2012] [Accepted: 01/13/2012] [Indexed: 01/13/2023]
Abstract
We investigated the behavioural effects of short-term lead (Pb) exposure in adult rats producing blood Pb concentration (<10 μg/dL) below those associated with neurological impairment in occupationally exposed individuals. In order to assess gender differences, we performed parallel behavioural experiments in male and female rats. Exposure to Pb acetate (50 mg/L in drinking water) for 30-45 days induced behavioural alterations consisting in hyperactivity in a novel environment and impairment of spatial memory. These effects were observed only in male rats. Object recognition, motor coordination were unaffected by Pb exposure. Magnetic resonance spectroscopy allows in vivo assessment of main brain metabolites (glutamate/glutamine, creatine, myoinositol, N-acetylaspartate and choline) whose changes have been demonstrated in several central nervous system pathologies. Exposure to Pb did not affect metabolite profile in the striatum and increase myoinositol signal in the hippocampus of male rats. The increase in myoinositol in hippocampus suggests early Pb-induced alteration in glial metabolism in this brain region and may represent a potential marker of early brain dysfunction during Pb exposure.
Collapse
|
|
22
|
Wylezinska M, Cobbold JFL, Fitzpatrick J, McPhail MJW, Crossey MME, Thomas HC, Hajnal JV, Vennart W, Cox IJ, Taylor-Robinson SD. A comparison of single-voxel clinical in vivo hepatic 31P MR spectra acquired at 1.5 and 3.0 Tesla in health and diseased states. NMR IN BIOMEDICINE 2011; 24:231-7. [PMID: 20949641 DOI: 10.1002/nbm.1578] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2009] [Revised: 05/15/2010] [Accepted: 05/17/2010] [Indexed: 05/30/2023]
Abstract
With the increasing availability of human MR scanners at various field strengths, the optimal field strength for in vivo clinical MR studies of the liver has become a focus of attention. Comparison between results at 3.0 and 1.5 T is of particular clinical interest, especially for multicentre studies. For MRS studies, higher field strengths should be advantageous, because improved sensitivity and chemical shift dispersion are expected. We report a comparison between single-voxel hepatic proton-decoupled (31)P MRS performed at 1.5 and 3.0 T in the same subjects using similar methodologies. Twelve healthy volunteers and 15 patients with chronic liver disease were studied. Improved spectral resolution was achieved using proton decoupling, and there was an improvement (21%) in the signal-to-noise ratio (SNR) of the phosphomonoester (PME) resonance at 3.0 T relative to 1.5 T. There was no significant change in nuclear Overhauser effects for PME or phosphodiesters (PDEs) between the two field strengths. The T(1) value of PDE was significantly longer at 3 T, although there was no significant change in the T(1) value of PME. There was no significant difference in the mean PME/PDE ratios for either the control or patient groups at both 1.5 and 3.0 T, but there was a small positive mean difference in PME/PDE at 3.0 T on pairwise testing between field strengths (+ 0.05, p < 0.01). There were significant correlations between PME/PDE values at the two magnetic field strengths (r = 0.806, p < 0.001). The underlying broad resonance was reduced at 3.0 T relative to 1.5 T, related to line broadening of the phospholipid bilayer signal. In conclusion, there was an improvement in hepatic (31)P MR signal quality at 3.0 T relative to 1.5 T. Broadly similar hepatic (31)P MR parameters were obtained at 1.5 and 3.0 T. The modest difference noted in the PME/PDE ratio between field strengths for patients with chronic liver disease should inform multicentre study design involving these field strengths.
Collapse
Affiliation(s)
- Marzena Wylezinska
- Hepatology and Gastroenterology Section, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, St Mary's Campus, Faculty of Medicine, Imperial College London, London, UK
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Patel KD, Abeysekera KWM, Marlais M, McPhail MJW, Thomas HC, Fitzpatrick JA, Lim AKP, Taylor-Robinson SD, Thomas EL. Recent advances in imaging hepatic fibrosis and steatosis. Expert Rev Gastroenterol Hepatol 2011; 5:91-104. [PMID: 21309675 DOI: 10.1586/egh.10.85] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Liver disease is an increasing cause of morbidity and mortality worldwide. Currently, the gold standard for diagnosis and assessment of parenchymal disease is histopathological assessment of a percutaneous or transjugular liver biopsy. The risks and limitations of this technique are well recognized and as a result, significant effort has gone into the development of novel noninvasive methods of diagnosis and longitudinal assessment. Imaging techniques have improved significantly over the past decade and new technologies are beginning to enter clinical practice. Ultrasound, computed tomography and MRI are the main modalities currently used, but novel MRI-based techniques will have an increasing role. While there has been extensive research into the imaging of focal liver disease, the evidence base for imaging in diffuse disease has also undergone recent rapid development, particularly in the assessment of fibrosis and steatosis. Both of these abnormalities of the parenchyma can lead to cirrhosis and/or hepatocellular carcinoma and represent an important opportunity for detection of early liver disease. We discuss the recent advances in liver imaging techniques and their role in the diagnosis and monitoring of diffuse liver disease, with a focus on their current and potential clinical relevance and whether they may replace or augment liver biopsy. We also discuss techniques currently under development and their potential clinical applications in the future.
Collapse
Affiliation(s)
- Kayur D Patel
- Liver Unit, Division of Diabetes Endocrinology and Metabolism, Department of Medicine, 10th Floor Queen Elizabeth the Queen Mother Wing, St Mary's Hospital Campus, Imperial College London, South Wharf Street, London W2 1NY, UK
| | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
McPhail MJW, Taylor-Robinson SD. The role of magnetic resonance imaging and spectroscopy in hepatic encephalopathy. Metab Brain Dis 2010; 25:65-72. [PMID: 20221679 DOI: 10.1007/s11011-010-9171-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2009] [Accepted: 01/28/2010] [Indexed: 01/22/2023]
Abstract
Hepatic encephalopathy (HE) is a diverse manifestation of acute and chronic liver failure, ranging from cognitive impairment, only detectable on psychometric evaluation through to confusion, coma and death from cerebral oedema. While there is widespread acceptance of its importance, there is little consensus on how best to diagnose and monitor HE. Clinical descriptions, psychometric testing, electroencephalography and magnetic resonance (MR) imaging (and lately, MR spectroscopy) have all been proposed. MR techniques, in contrast to other modalities, have the benefit of objectivity and of being able to interrogate the brain directly with respect to changes in brain size, function and the metabolic disturbances thought to underlie HE, particularly in the context of astrocyte swelling. Modern clinical MRI scanners with multinuclear MR spectroscopy capabilities and brain mapping software can demonstrate structural and functional cellular changes using volumetric MRI, magnetization transfer MRI, diffusion-weighting MRI, functional MRI with oxygenation measurements and in vivo and in vitro (1)H and (31)P MR spectroscopy. This review describes the relative merits of these techniques and provides guidance on the directions for future research and translation into clinical practice.
Collapse
Affiliation(s)
- Mark J W McPhail
- Liver and Anti-Viral Centre, Department of Hepatology, Division of Medicine, Imperial College London, 10th Floor QEQM Building, St Mary's Hospital Campus, South Wharf Road, London, W2 1NY, United Kingdom
| | | |
Collapse
|
|
25
|
Kim HW, Lee D, Pohost GM. (31)P cardiovascular magnetic resonance spectroscopy: a unique approach to the assessment of the myocardium. Future Cardiol 2010; 5:523-7. [PMID: 19886777 DOI: 10.2217/fca.09.40] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
|
|
26
|
Aaronson DS, Iman R, Walsh TJ, Kurhanewicz J, Turek PJ. A novel application of 1H magnetic resonance spectroscopy: non-invasive identification of spermatogenesis in men with non-obstructive azoospermia. Hum Reprod 2010; 25:847-52. [PMID: 20124393 DOI: 10.1093/humrep/dep475] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND About 10% of infertile men have no sperm in their ejaculate due to poor or absent spermatogenesis, also known as non-obstructive azoospermia (NOA). Testis (1)H magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive imaging tool that can potentially identify and localize spermatogenesis in the testis. This study sought to identify metabolic signatures associated with various histological states of spermatogenesis in infertile men. METHODS Quantitative high resolution magic angle spinning spectroscopy was performed on snap frozen testicular tissue from 27 men with three classic histological patterns: (i) normal spermatogenesis (men with prior paternity undergoing vasectomy reversal), (ii) maturation arrest (early or late, MA) or (iii) Sertoli-cell only (SCO). Concentrations of 19 tissue metabolites were acquired from each biopsy specimen. One-way ANOVA analysis was used to determine inter-group differences in metabolite concentrations among the three histologic groups. RESULTS Phosphocholine (PC) and taurine tissue concentrations were significantly different between normal and SCO tissue. Mean PC concentrations were three times higher in normal testes compared with SCO (5.4 +/- 1.4 versus 1.5 +/- 0.3 mmol/kg; P = 0.01). No differences in metabolite concentrations were observed between normal and MA testes or between SCO and MA testes. Further histologic stratification of MA testes into subsets of those with (early) and without (late) spermatids or mature sperm, identified differences in PC concentrations. A predictive model for sperm presence with (1)H-MRS was developed based upon PC tissue concentrations. CONCLUSIONS PC concentrations are significantly higher in testes with spermatogenesis. This suggests that a unique metabolic signature for spermatogenesis is possible using (1)H-MRS which could aid in the non-invasive diagnosis of sperm in men with NOA.
Collapse
Affiliation(s)
- David S Aaronson
- Department of Urology, University of California San Francisco, Ambulatory Care Center, Suite A633, San Francisco, CA 94117, USA.
| | | | | | | | | |
Collapse
|
|
27
|
Hsieh TJ, Chen YC, Li CW, Liu GC, Chiu YW, Chuang HY. A proton magnetic resonance spectroscopy study of the chronic lead effect on the Basal ganglion and frontal and occipital lobes in middle-age adults. ENVIRONMENTAL HEALTH PERSPECTIVES 2009; 117:941-945. [PMID: 19590687 PMCID: PMC2702410 DOI: 10.1289/ehp.0800187] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2008] [Accepted: 02/09/2009] [Indexed: 05/28/2023]
Abstract
BACKGROUND Lead is known to be a health hazard to the human brain and nervous system based on data from epidemiologic studies. However, few studies have examined the mechanism or biochemical changes caused by lead in the human brain, although recently some have used magnetic resonance spectroscopy (MRS) to test brain metabolism in vivo. OBJECTIVES In this study, we used 3-T MRS to investigate brain metabolism in workers chronically exposed to lead and matched nonexposed controls. METHODS Twenty-two workers at a lead paint factory served as chronically exposed subjects of this study. These workers did not have any clinical syndromes. Eighteen age- and sex-matched nonexposed healthy volunteers served as controls. We measured blood and bone lead and used a 3-T MRS to measure their levels of brain N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr). A structural questionnaire was used to collect demographic, work, and health histories and information about their life habits. RESULTS All the MRS measures were lower in the lead-exposed group. Increased blood and bone lead levels correlated with declines in Cho:tCr ratios, especially in the occipital lobe, where changes in all gray, subcortical, and white matter were significant. Increases in blood and patella lead in every layer of the frontal lobe correlated with significant decreases in NAA:tCr ratios. One of the strongest regression coefficients was -0.023 (SE = 0.005, p < 0.001), which was found in the NAA:tCr ratio of frontal gray matter. DISCUSSION We conclude that chronic exposure to lead might upset brain metabolism, especially NAA:tCr and Cho:tCr ratios. Brain NAA and Cho are negatively correlated to blood and bone lead levels, suggesting that lead induces neuronal and axonal damage or loss. The most significant changes occurred in frontal and occipital lobes, areas in which previous neurobehavioral studies have shown memory and visual performance to be adversely affected by lead toxicity.
Collapse
Affiliation(s)
| | - Yi-Chun Chen
- Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
| | - Chun-Wei Li
- Department of Medical Imaging and Radiation Technology, College of Health Sciences and
| | - Gin-Chang Liu
- Department of Medical Imaging and
- Department of Radiology, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Yu-Wen Chiu
- Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
| | - Hung-Yi Chuang
- Department of Community Medicine, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan
- Department of Public Health, College of Health Sciences, and Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
| |
Collapse
|
|
28
|
Liu J, Segal M, Yoo S, Yang GY, Kelly M, James TL, Litt L. Antioxidant effect of ethyl pyruvate in respiring neonatal cerebrocortical slices after H(2)O(2) stress. Neurochem Int 2009; 54:106-10. [PMID: 19041675 DOI: 10.1016/j.neuint.2008.10.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2008] [Revised: 10/13/2008] [Accepted: 10/23/2008] [Indexed: 11/19/2022]
Abstract
Administration of ethyl pyruvate, which is formed from pyruvate and ethanol, has been found capable of rescuing cells injured by oxidative stress. In one perspective the rescue has been postulated to be metabolic, with the resulting intracellular delivery of pyruvate seen as providing substrate for the TCA Cycle, making it possible to counteract sequela of poly(ADP-ribose)ribosylation, such as depletion of cytosolic NAD(+), glycolytic arrest, and mitochondrial deprivation of pyruvate. The rescue has also been attributed to radical scavenging via the carbonyl groups in ethyl pyruvate and pyruvate. In a previous study we exposed superfused neonatal (P7) brain slices for 60min to 2mM H(2)O(2) and found evidence for both rescue mechanisms. To see if ethyl pyruvate's actions stemmed more from being an antioxidant than from being a nutrient we conducted six new experiments using the same H(2)O(2) protocol, but with two new rescue solutions: [10mM] glucose (glc) plus one of the following: ethyl pyruvate [20mM], or the nonmetabolizable radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN, 1mM). Final ATP values compared to initial, measured in 14.1T (31)P NMR spectra of PCA extracts, were the same: 0.70+/-0.08 for the former (N=3), and 0.64+/-0.08 for the latter (N=3). Quantifications of this study's (1)H NMR metabolites, also measured at 14.1T, exhibited separate clustering when pooled with data from the previous study and compared in a metabolomic multivariate analyses. Because the addition of ethyl pyruvate provided the same ATP protection as the addition of a nonmetabolizable antioxidant, antioxidant protection was its prominent protective mechanism in the chosen, high glucose protocol. Having distinct clusters in the Scores Plot of a Partial Least Squares-Discriminant Analysis suggests the feasibility of constructing statistical models that are predictive.
Collapse
Affiliation(s)
- J Liu
- Department of Anesthesia, The University of California San Francisco, San Francisco 94143-0648, United States
| | | | | | | | | | | | | |
Collapse
|
|
29
|
Tshibanda L, Vanhaudenhuyse A, Galanaud D, Boly M, Laureys S, Puybasset L. Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls. PROGRESS IN BRAIN RESEARCH 2009; 177:215-29. [PMID: 19818904 DOI: 10.1016/s0079-6123(09)17715-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The status of comatose patient is currently established on the basis of the patient-exhibited behaviors. Clinical assessment is subjective and, in 40% of patients, fails to distinguish vegetative state (VS) from minimally conscious states (MCS). The technologic advances of magnetic resonance imaging (MRI) have dramatically improved our understanding of these altered states of consciousness. The role of neuroimaging in coma survivors has increased beyond the simple evaluation of morphological abnormalities. The development of 1H-MR spectroscopy (MRS) and diffusion tensor imaging (DTI) provide opportunity to evaluate processes that cannot be approached by current morphologic MRI sequences. They offer potentially unique insights into the histopathology of VS and MCS. The MRS is a powerful noninvasive imaging technique that enables the in vivo quantification of certain chemical compound or metabolites as N-acetylaspartate (NAA), Choline (Cho), and Creatine (Cr). These biomarkers explore neuronal integrity (NAA), cell membrane turnover (Cho), and cell energetic function (Cr). DTI is an effective and proved quantitative method for evaluating tissue integrity at microscopic level. It provides information about the microstructure and the architecture of tissues, especially the white matter. Various physical parameters can be extracted from this sequence: the fractional anisotropy (FA), a marker of white matter integrity; mean diffusivity (MD); and the apparent diffusion coefficient (ADC) which can differentiate cytotoxic and vasogenic edema. The most prominent findings with MRS and DTI performed in traumatic brain-injured (TBI) patients in subacute phase are the reduction of the NAA/Cr ratio in posterior pons and the decrease of mean infratentorial and supratentorial FA except in posterior pons that enables to predict unfavorable outcome at 1 year from TBI with up to 86% sensitivity and 97% specificity. This review will focus on the interest of comatose patients MRI multimodal assessment with MRS and DTI. It will emphasize the advantages and pitfalls of these techniques in particular in predicting the coma survivors' outcome.
Collapse
Affiliation(s)
- Luaba Tshibanda
- Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Belgium
| | | | | | | | | | | |
Collapse
|
|
30
|
Roldan-Valadez E, Favila R, Martínez-López M, Uribe M, Méndez-Sánchez N. Imaging techniques for assessing hepatic fat content in nonalcoholic fatty liver disease. Ann Hepatol 2008; 7:212-220. [PMID: 18753987 DOI: 10.1016/s1665-2681(19)31850-2] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), an emerging clinical entity with worldwide recognition, is today the most common cause of abnormal liver function tests among adults in the United States. In Mexico City, its prevalence has been reported by our group to be around 14%, but its incidence is higher in the hispanic population in the United States (hispanic population 45%, white population 33%, black population 24%). The main issues in the diagnosis, follow-up, and management of NAFLD are our limited understanding of its pathophysiology and the difficulties involved in developing a noninvasive diagnostic method. Several imaging techniques can detect fatty infiltration of the liver, each with its own advantages and disadvantages. Ultrasound is still in the first option for diagnosis, but its accuracy depends on the operator and the patient's features. Computed tomography can detect hepatic fat content, but only at a threshold of 30%, and it involves ionizing radiation. Magnetic resonance (MR) spectroscopy is probably the most accurate and fastest method of detecting fat, but it is expensive and the necessary software is still not easily available in most MRI units. MR elastography, a new technique to detect liver stiffness, has not been demonstrated to detect NAFLD, and is still undergoing research in patients with hepatitis and cirrhosis. In conclusion, all these imaging tools are limited in their ability to detect coexisting inflammation and fibrosis. In this review, we discuss the radiological techniques currently used to detect hepatic fat content.
Collapse
|
|
31
|
Mehta SR, Thomas EL, Bell JD, Johnston DG, Taylor-Robinson SD. Non-invasive means of measuring hepatic fat content. World J Gastroenterol 2008; 14:3476-83. [PMID: 18567074 PMCID: PMC2716608 DOI: 10.3748/wjg.14.3476] [Citation(s) in RCA: 196] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2007] [Revised: 12/14/2007] [Accepted: 12/21/2007] [Indexed: 02/06/2023] Open
Abstract
Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance (MR) techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo (1)H MRS is a fast, safe, non-invasive method for the quantification of intrahepatocellular lipid (IHCL) levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis (e.g. non-alcoholic fatty liver disease), or in testing new treatments for these conditions.
Collapse
|
|
32
|
Treasaden IH, Puri BK. Cerebral spectroscopic and oxidative stress studies in patients with schizophrenia who have dangerously violently offended. BMC Psychiatry 2008; 8 Suppl 1:S7. [PMID: 18433517 PMCID: PMC2330075 DOI: 10.1186/1471-244x-8-s1-s7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The aim of this study was to bring together all the results of in vivo studies of ethane excretion and cerebral spectroscopy in patients with schizophrenia who have dangerously seriously violently offended in order to determine the extent to which they shed light on the degree to which the membrane phospholipid hypothesis and the actions of free radicals and other reactive species are associated with cerebral pathophysiological mechanisms in this group of patients. METHODS The patients investigated were inpatients from a medium secure unit with a DSM-IV-TR diagnosis of schizophrenia. There was no history of alcohol dependency or any other comorbid psychoactive substance misuse disorder. Expert psychiatric opinion, accepted in court, was that all these patients had violently offended directly as a result of schizophrenia prior to admission. These offences consisted of homicide, attempted murder or wounding with intent to cause grievous bodily harm. Excreted ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). 31-phosphorus magnetic resonance spectroscopy data were obtained at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 x 70 x 70 mm3 voxel). RESULTS Compared with age- and sex-matched controls, in the patient group the mean alveolar ethane level was higher (p < 0.0005), the mean cerebral beta-nucleotide triphosphate was lower (p < 0.04) and the mean gamma-nucleotide triphosphate was higher (p < 0.04). There was no significant difference between the two groups in respect of phosphomonoesters, phosphodiesters or broad resonances. CONCLUSION Our results are not necessarily inconsistent with the membrane phospholipid hypothesis, given that the patients studied suffered predominantly from positive symptoms of schizophrenia. The results suggest that there is increased cerebral mitochondrial oxidative phosphorylation in patients with schizophrenia who have dangerously and seriously violently offended, with an associated increase in oxygen flux and subsequent electron 'leakage' from the electron transport chain leading to the formation of superoxide radicals and other reactive oxygen species. In turn, these reactive species might cause increased lipid peroxidation in neuroglial membranes, thereby accounting for the observation of increased ethane excretion.
Collapse
Affiliation(s)
- Ian H Treasaden
- Three Bridges Medium Secure Unit, West London Mental Health NHS Trust, Uxbridge Road, Southall, Middlesex UB1 3EU, UK.
| | - Basant K Puri
- MRI Unit, MRC Clinical Sciences Centre, Imaging Sciences Department, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| |
Collapse
|
|
33
|
Abstract
With increased availability of magnetic resonance (MR) systems at ultra-high field strength for clinical studies, other organs besides the brain have received renewed consideration for MR spectroscopy (MRS). Because signal-to-noise ratio and chemical shift increase proportional to the static magnetic field, a concomitant increase in signal intensity and spectral resolution of metabolite resonances can be exploited. Improved resolution of adjacent metabolite peaks would not only provide for more accuracy of metabolite identification but also metabolite quantification. While the superiority of high-field imaging and spectroscopy has already been demonstrated clearly in the brain, this article reviewed issues around 1H MRS of the liver. These include optimization strategies such as coil technology, minimizing of motion artefacts using breath-holding and postprocessing of the spectra. Moreover, we reviewed the pertinent experience hitherto reported in the literature on potential clinical issues where liver MRS may be useful. These included determination and characterization of liver fat content, liver tumours and focal lesions. While these applications have been used experimentally, liver MRS does not yet have a clearly defined role in the clinical management of any disease state. Accordingly, it remains primarily a research modality to date.
Collapse
Affiliation(s)
- Frank Fischbach
- Department of Radiology and Nuclear Medicine, Medical School, Otto von Guenicke University, Magdeburg, Germany.
| | | |
Collapse
|
|
34
|
Talwalkar JA, Yin M, Fidler JL, Sanderson SO, Kamath PS, Ehman RL. Magnetic resonance imaging of hepatic fibrosis: emerging clinical applications. Hepatology 2008; 47:332-42. [PMID: 18161879 DOI: 10.1002/hep.21972] [Citation(s) in RCA: 227] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Chronic liver disease and cirrhosis remains a major public health problem worldwide. While the majority of complications from chronic liver disease result from progressive hepatic fibrosis, the available diagnostic tests used in clinical practice are not sensitive or specific enough to detect occult liver injury at early or intermediate stages. While liver biopsy can stage the extent of fibrosis at diagnosis, its utility as a tool for longitudinal monitoring will be limited at the population level. To date, a number of methods including serum marker panels and ultrasound-based transient elastrography have been proposed for the non-invasive identification of hepatic fibrosis. Novel techniques including magnetic resonance (MR) spectroscopy, diffusion weighted MR, and MR elastography have also emerged for detecting fibrosis. In contrast to other non-invasive methods, MR imaging holds the promise of providing functional and biological information about hepatic pathophysiology as it relates to the natural history and future treatment of hepatic fibrosis. (HEPATOLOGY 2007.).
Collapse
Affiliation(s)
- Jayant A Talwalkar
- Advanced Liver Diseases Study Group, Miles and Shirley Fitterman Center for Digestive Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA.
| | | | | | | | | | | |
Collapse
|
|
35
|
Noren B, Dahlqvist O, Lundberg P, Almer S, Kechagias S, Ekstedt M, Franzén L, Wirell S, Smedby O. Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy. Eur J Radiol 2007; 66:313-20. [PMID: 17646074 DOI: 10.1016/j.ejrad.2007.06.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2006] [Revised: 05/08/2007] [Accepted: 06/04/2007] [Indexed: 12/12/2022]
Abstract
31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, gammaATP, alphaATP, betaATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n=13), and one group with severe fibrosis or cirrhosis (n=16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n=13) was also included. Absolute concentrations and the anabolic charge, AC=[PME]/([PME]+[PDE]), were calculated. Comparing the control and cirrhosis groups, lower concentrations of PDE (p=0.025) and a higher AC (p<0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p=0.01) and a higher AC (p=0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0-1 and stage F4 and in AC between stage F0-1 and stage F2-3. Using a PDE concentration of 10.5mM as a cut-off value to discriminate between mild, F0-2, and advanced, F3-4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%. In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.
Collapse
Affiliation(s)
- Bengt Noren
- Department of Radiology, Linköping University, SE-581 85 Linköping, Sweden
| | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Cox IJ, Sharif A, Cobbold JFL, Thomas HC, Taylor-Robinson SD. Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease. World J Gastroenterol 2006; 12:4773-83. [PMID: 16937457 PMCID: PMC4087609 DOI: 10.3748/wjg.v12.i30.4773] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiological processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response.
Collapse
Affiliation(s)
- I Jane Cox
- Imaging Sciences Department, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
| | | | | | | | | |
Collapse
|
|
37
|
Wang SJ, Lirng JF, Fuh JL, Chen JJ. Reduction in hypothalamic 1H-MRS metabolite ratios in patients with cluster headache. J Neurol Neurosurg Psychiatry 2006; 77:622-5. [PMID: 16614022 PMCID: PMC2117468 DOI: 10.1136/jnnp.2005.081836] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2005] [Revised: 11/23/2005] [Accepted: 12/07/2005] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To determine the 1H-MR spectroscopic (MRS) findings in the hypothalamus in patients with episodic cluster headache. METHODS 47 patients were recruited with episodic cluster headache (35 in cluster period and 12 in remission), 21 normal controls, and 16 patients with chronic migraine. The hypothalamic 1H-MRS metabolite ratio changes in patients with cluster headache were evaluated and compared with results in the normal controls as well as patients with chronic migraine. Seven patients in the cluster period group underwent a follow up hypothalamic MRS study five to six months after remission. RESULTS In patients with cluster headache, the hypothalamic N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were similar between those in cluster period and in remission. As a group, both NAA/Cr and Cho/Cr levels were significantly lower in patients with cluster headache in comparison with either the control or chronic migraine groups. In those with a follow up MRS study, the levels of metabolite ratios did not differ between the cluster and remission periods. CONCLUSIONS This study provides evidence of persistent biochemical change of the hypothalamus in patients with episodic cluster headache. Low levels of NAA/Cr and Cho/Cr suggest that cluster headache might be related to both neuronal dysfunction and changes in the membrane lipids in the hypothalamus.
Collapse
Affiliation(s)
- S-J Wang
- Neurological Institute, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan, 112.
| | | | | | | |
Collapse
|
|
38
|
Khan SA, Cox IJ, Thillainayagam AV, Bansi DS, Thomas HC, Taylor-Robinson SD. Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer. Eur J Gastroenterol Hepatol 2005; 17:733-8. [PMID: 15947550 DOI: 10.1097/00042737-200507000-00007] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE Hepatopancreaticobiliary cancers can be difficult to diagnose. Nuclear magnetic resonance (NMR) spectroscopy provides non-invasive information on phospholipid metabolism, and previous studies of liver tissue have highlighted changes in phospholipids in malignancy. We hypothesised that in-vitro NMR spectroscopy of human bile may provide independent diagnostic indices in cancer management through an assessment of the phospholipid content. DESIGN AND METHODS Bile samples from 24 patients were collected at endoscopic retrograde cholangiopancreatography and from one subject at cholecystectomy. Thirteen patients had cancer: pancreatic carcinoma (eight), cholangiocarcinoma (three) and metastatic liver disease (two). The remaining 12 patients had non-malignant pathology. In-vitro proton (H) and phosphorus-31 (P) NMR spectra were obtained from all samples using an 11.7 Tesla NMR spectroscopy system. RESULTS Complementary information was obtained from the H and P NMR spectra. Signals were assigned to phosphatidylcholine in both H and P NMR spectra. Phosphatidylcholine levels were significantly reduced in the bile from cancer patients when compared with bile from non-cancer patients (P=0.007). CONCLUSION These preliminary studies suggest that H and P NMR spectroscopy of bile may be used to detect differences in phospholipid content between cancer and non-cancer patients. This may have implications for the development of novel diagnostic strategies in hepatopancreaticobiliary cancers. Further larger-scale studies are warranted.
Collapse
Affiliation(s)
- Shahid A Khan
- Liver Unit, Division of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK.
| | | | | | | | | | | |
Collapse
|
|
39
|
Sarac K, Akinci A, Alkan A, Aslan M, Baysal T, Ozcan C. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus. Neuroradiology 2005; 47:562-5. [PMID: 15973536 DOI: 10.1007/s00234-005-1387-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2004] [Accepted: 02/04/2005] [Indexed: 11/29/2022]
Abstract
The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9 +/- 3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9 +/- 2.2 (0-9) and the average number of daily insulin injections was 2.8 +/- 0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover.
Collapse
Affiliation(s)
- K Sarac
- Department of Radiology, Inonu University School of Medicine, Turgut Ozal Tip Merkezi, Malatya, Turkey.
| | | | | | | | | | | |
Collapse
|
|
40
|
Ratai EM, Pilkenton S, Lentz MR, Greco JB, Fuller RA, Kim JP, He J, Cheng LL, González RG. Comparisons of brain metabolites observed by HRMAS 1H NMR of intact tissue and solution 1H NMR of tissue extracts in SIV-infected macaques. NMR IN BIOMEDICINE 2005; 18:242-51. [PMID: 15759297 DOI: 10.1002/nbm.953] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The objective of this study was to compare ex vivo proton high-resolution magic angle spinning magnetic resonance spectra of intact tissue with those spectra obtained by solution (1)H NMR of brain extracts of the same sample. Sixteen brain tissue samples from simian immunodeficiency virus-infected rhesus macaques from both frontal cortex and putamen were evaluated by comparing brain metabolite quantities of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (MI), creatine (Cr), lactate (Lac), glutamate (Glu) and acetate (Ace). The ratios of the individual NMR peak areas of all metabolites relative to the creatine peak area were calculated. Linear regression analysis revealed significant correlations between measurements using the two methods. The strength of the correlations varied depending on the metabolite studied. We found highly significant correlations for NAA/Cr (r2 = 0.77; p < 0.0001), NAA + Ace/Cr (r2 = 0.73; p < 0.0001) and MI/Cr (r2 = 0.75; p < 0.0001). We observed somewhat less strong correlations for Glu/Cr (r2 = 0.54; p < 0.002) and Lac/Cr (r2 = 0.54; p < 0.002). There was a substantially weaker correlation for Cho/Cr (r2 = 0.32; p = 0.02). When plotting the metabolite ratios obtained by 1H HRMAS NMR of the intact tissue sample on the ordinate vs 1H NMR of the tissue extract on the abscissa, most metabolites exhibited a slope close to unity, and a positive intercept probably due to macromolecular contributions to the MAS spectra. The slope for Cho/Cr was substantially less than unity. Generally, samples from the frontal cortex showed a better correlation between intact and extracted tissue samples than putamen. This is most prominent in the cases of NAA/Cr and Cho/Cr. We conclude that both methods provide substantially the same information for most major brain metabolites, with the exception of the Cho resonance.
Collapse
Affiliation(s)
- Eva M Ratai
- Massachusetts General Hospital NMR Center and Neuroradiology Division, 149 13th St, Charlestown, MA 02129, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Abstract
There is compelling evidence that alterations in myocardial substrate use play a key role in a variety of normal and abnormal cardiac conditions such as aging, left ventricular hypertrophy, and diabetic heart disease. However, it is unclear whether the metabolic changes are adaptive or maladaptive. Development of transgenic models targeting key aspects of myocardial substrate use, such as uptake, oxidation, and storage, is accelerating our understanding of the metabolic perturbations of cardiac disease. However, whether the metabolic phenotype in these models is relevant to the human condition is frequently unknown. The importance of altered myocardial metabolism in the pathogenesis of cardiac disease is underscored by the current robust development of novel therapeutics that target myocardial substrate use. Currently, magnetic resonance spectroscopy, single photon emission computed tomography, and positron emission tomography are the 3 methods available to image myocardial substrate metabolism. In this review the role of metabolic imaging in the study of specific cardiac disease processes will be discussed. Both the current and future capabilities of metabolic imaging to furthering our understanding of cardiac disease are highlighted.
Collapse
Affiliation(s)
- Pilar Herrero
- Division of Radiological Sciences, Mallinckrodt Institute of Radiology, St Louis, MO 63110, USA
| | | |
Collapse
|
|
42
|
Khan SA, Cox IJ, Hamilton G, Thomas HC, Taylor-Robinson SD. In vivo and in vitro nuclear magnetic resonance spectroscopy as a tool for investigating hepatobiliary disease: a review of H and P MRS applications. Liver Int 2005; 25:273-81. [PMID: 15780050 DOI: 10.1111/j.1478-3231.2005.01090.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive technique, which allows the study of cellular biochemistry and metabolism. It is a diverse research tool, widely used by biochemists to investigate pathophysiological processes in vitro and, more recently, by physicians to determine disease abnormalities in vivo. This article reviews the basics of the NMR phenomenon and summarises previous research on the hepatobiliary system using both laboratory-based and clinical methodologies. The role of proton and phosphorus-31 ((31)P) NMR spectroscopy in the study of malignant and non-malignant liver disease and studies of bile composition are discussed. In vivo techniques (magnetic resonance spectroscopy, MRS) can be performed as an adjunct to standard MR examination of the liver. Although still primarily a research tool, the in vivo technique provides non-invasive biochemical information on disease severity and holds promise in its use to gauge response to treatment regimens.
Collapse
Affiliation(s)
- Shahid A Khan
- Liver Unit, Department of Medicine A, St Mary's Hospital Campus, Imperial College London, 10th Floor, QEQM Building, London W2 1NY, UK.
| | | | | | | | | |
Collapse
|
|
43
|
Norén B, Lundberg P, Ressner M, Wirell S, Almer S, Smedby O. Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease. Eur Radiol 2004; 15:148-57. [PMID: 15351899 DOI: 10.1007/s00330-004-2434-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2003] [Revised: 06/04/2004] [Accepted: 06/28/2004] [Indexed: 12/13/2022]
Abstract
Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3+/-3.9 mM, and ATP-beta, 3.6+/-1.1 mM, (P<0.05) compared with the control group (10.0+/-4.2 mM and 4.2+/-0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.
Collapse
Affiliation(s)
- Bengt Norén
- Depatment of Radiology/IMV, Linköping University, 581-85 Linköping, Sweden
| | | | | | | | | | | |
Collapse
|
|
44
|
Corbin IR, Ryner LN, Singh H, Minuk GY. Quantitative hepatic phosphorus-31 magnetic resonance spectroscopy in compensated and decompensated cirrhosis. Am J Physiol Gastrointest Liver Physiol 2004; 287:G379-84. [PMID: 15191882 DOI: 10.1152/ajpgi.00418.2003] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Few studies have examined the physiological/biochemical status of hepatocytes in patients with compensated and decompensated cirrhosis in situ. Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is a noninvasive technique that permits direct assessments of tissue bioenergetics and phospholipid metabolism. Quantitative (31)P MRS was employed to document differences in the hepatic metabolite concentrations among patients with compensated and decompensated cirrhosis as well as healthy controls. All MRS examinations were performed on a 1.5-T General Electric Signa whole body scanner. The concentration of hepatic phosphorylated metabolites among patients with compensated cirrhosis (n = 7) was similar to that among healthy controls (n = 8). However, patients with decompensated cirrhosis (n = 6) had significantly lower levels of hepatic ATP compared with patients with compensated cirrhosis and healthy controls (P < 0.02 and P < 0.009, respectively) and a higher phosphomonoester/phosphodiester ratio than controls (P < 0.003). The results of this study indicate that metabolic disturbances in hepatic energy and phospholipid metabolism exist in patients with decompensated cirrhosis that are not present in patients with compensated cirrhosis or healthy controls. These findings provide new insights into the pathophysiology of hepatic decompensation.
Collapse
Affiliation(s)
- I R Corbin
- John Buhler Research Centre, 803F-715 McDermot Ave., Winnipeg, Manitoba, Canada.
| | | | | | | |
Collapse
|
|
45
|
Cox IJ, Puri BK. In vivo MR spectroscopy in diagnosis and research of neuropsychiatric disorders. Prostaglandins Leukot Essent Fatty Acids 2004; 70:357-60. [PMID: 15041027 DOI: 10.1016/j.plefa.2003.12.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2003] [Indexed: 12/19/2022]
Abstract
Magnetic resonance spectroscopy is one of the most important tools for quantitative analysis of chemical composition and structure, and this non-invasive technique is now being applied in vivo to study biochemical processes in those neuropsychiatric disorders that are part of the phospholipid spectrum. Interpretation of a clinical magnetic resonance spectrum can provide information about membrane phospholipid turnover, cellular energetics, neuronal function, selected neurotransmitter activity and intracellular pH. Cerebral proton and phosphorus magnetic resonance spectroscopy findings are summarized in relation to schizophrenia, dyslexia and chronic fatigue syndrome.
Collapse
Affiliation(s)
- I J Cox
- Faculty of Medicine, Imaging Sciences Department, Imperial College London, Division of Clinical Sciences, Robert Steiner Magnetic Resonance Unit, Hammersmith Campus, Du Cane Road, London W12 0HS, UK.
| | | |
Collapse
|
|
46
|
Puri BK, Counsell SJ, Hamilton G, Bustos MG, Horrobin DF, Richardson AJ, Treasaden IH. Cerebral metabolism in male patients with schizophrenia who have seriously and dangerously violently offended: a 31P magnetic resonance spectroscopy study. Prostaglandins Leukot Essent Fatty Acids 2004; 70:409-11. [PMID: 15041035 DOI: 10.1016/j.plefa.2003.12.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2003] [Indexed: 11/17/2022]
Abstract
There is biochemical evidence to suggest that membrane phospholipid metabolism may be impaired in some patients with schizophrenia. The aim of this study was to test the hypothesis that patients with schizophrenia who have violently offended while psychotic suffer from changes in cerebral phospholipid metabolism. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 15 male patients with schizophrenia who had violently offended (homicide, attempted murder, or wounding with intent to cause grievous bodily harm) while psychotic and in a control group of 13 age-matched healthy male control subjects. Spectra were obtained from 70x70x70mm(3) voxels in the brain using an image-selected in vivo spectroscopy pulse sequence. betaNTP was lower (P < 0.04) and gammaNTP was higher (P < 0.04) in the patient group compared with the normal control group. Our results are suggestive of increased cerebral energy metabolism taking place in the forensic patients.
Collapse
Affiliation(s)
- B K Puri
- MRI Unit, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
| | | | | | | | | | | | | |
Collapse
|
|
47
|
Abstract
PURPOSE OF REVIEW This review introduces physiologists and clinical investigators to an ever-widening array of nuclear magnetic resonance applications. In particular, it highlights a multiple tracer technique that provides a comprehensive picture of metabolic processes within human liver. RECENT FINDINGS Magnetic resonance spectroscopy is an important technique for studying metabolism in the brain, liver, heart and skeletal muscle. One fundamental advantage is that the studies are inherently noninvasive, so time-dependent information can be obtained. For example, 31P nuclear magnetic resonance investigations indicate that greater maximal oxygen uptake and oxidative capacity in trained athletes can be partially attributed to adaptations enhancing the rates at which phosphocreatine and inorganic phosphate recover during stress. In-vivo measurements of lipids and glycogen by 1H and 13C spectroscopy demonstrate that accumulation of intracellular lipids and impaired rates of glycogen synthesis contribute to insulin resistance and type 2 diabetes mellitus. Similar techniques can be used to analyze blood and urine samples obtained during administration of 2H or 13C tracers to yield information that cannot be easily obtained by mass spectrometry. Additional information available from nuclear magnetic resonance yields a comprehensive picture of liver metabolic pathways from a single clinical study. SUMMARY A variety of magnetic resonance spectroscopy protocols have been validated and exploited for clinical studies, but relatively few investigators are comfortable with technical aspects of these protocols and utilize them for clinical research. Increased interaction between spectroscopists and other investigators is needed if the potential of nuclear magnetic resonance for studying in-vivo metabolism is to be fully realized.
Collapse
Affiliation(s)
- Robert L Dobbins
- Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Texas, USA.
| | | |
Collapse
|
|
48
|
Hamilton G, Patel N, Forton DM, Hajnal JV, Taylor-Robinson SD. Prior knowledge for time domain quantification of in vivo brain or liver 31P MR spectra. NMR IN BIOMEDICINE 2003; 16:168-176. [PMID: 12884361 DOI: 10.1002/nbm.821] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Prior knowledge is required when quantifying in vivo (31)P magnetic resonance spectra from the brain or liver. The prior knowledge system we have used models both the phosphomonoester and phosphodiester resonances as two peaks of equal linewidth and fixed relative chemical shift. The analysis of the data is carried out in the time domain, which allows the broad component of the spectra to be modelled. This prior knowledge method has been tested for analysis of in vivo (31)P MR spectra from the liver and brain and gives results consistent with other methods that are also used to analyse the spectra, but with reduced variability. This technique may be utilized for studies requiring serial MR spectroscopy examinations, before and after patient treatment.
Collapse
Affiliation(s)
- Gavin Hamilton
- Robert Steiner MR Unit, Imaging Sciences Department, MRC Clinical Sciences Centre Imperial College London, London, UK.
| | | | | | | | | |
Collapse
|
|
49
|
Corbin IR, Buist R, Volotovskyy V, Peeling J, Zhang M, Minuk GY. Regenerative activity and liver function following partial hepatectomy in the rat using (31)P-MR spectroscopy. Hepatology 2002; 36:345-53. [PMID: 12143042 DOI: 10.1053/jhep.2002.34742] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
The aim of the present study was to determine whether alterations in hepatic energy expenditure following partial hepatectomy (PHx), as documented by in vivo hepatic (31)P-MRS, correlate with standard parameters of hepatic regeneration and/or liver function. In addition, we sought to determine whether changes in hepatic energy levels are proportional to the extent of hepatic resection. Adult male Sprague-Dawley rats (4-7 per group) underwent a 40%, 70%, or 90% PHx or sham surgeries. Magnetic resonance spectroscopy (MRS) examinations were performed on each animal 24 or 48 hours thereafter. After MRS examinations, [(3)H]thymidine incorporation into hepatic DNA, proliferating cell nuclear antigen (PCNA) protein expression, and serum bilirubin determinations were performed on each rat. Twenty-four hours following surgery, rats that had undergone 70% PHx had unchanged adenosine triphosphate (ATP) levels but significantly lower ATP/inorganic phosphate (Pi) ratios (P <.05), whereas, at 48 hours post-PHx, both ATP and ATP/Pi levels were lower than in sham- and nonoperated controls (P <.05). Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [(3)H]thymidine incorporation (r = -0.61, P <.005), PCNA protein expression (r = -0.62, P <.005), and serum bilirubin (r = -0.49, P <.05). For rats that had undergone graded resections, depleted energy levels 48 hours post-PHx were proportional to the extent of resection, degree of enhanced regenerative activity, and liver dysfunction. In conclusion, (31)P-MRS-generated ATP/Pi index is a noninvasive, robust determination that correlates with standard parameters of hepatic regeneration and function.
Collapse
Affiliation(s)
- Ian R Corbin
- Liver Diseases Unit, Department of Medicine, University of Manitoba, Winnipeg, Canada
| | | | | | | | | | | |
Collapse
|
|
50
|
Hutchinson PJ, O'Connell MT, Kirkpatrick PJ, Pickard JD. How can we measure substrate, metabolite and neurotransmitter concentrations in the human brain? Physiol Meas 2002; 23:R75-109. [PMID: 12051319 DOI: 10.1088/0967-3334/23/2/202] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Cerebral injury and disease is associated with fundamental derangements in metabolism, with changes in the concentration of important substrates (e.g. glucose), metabolites (e.g. lactate) and neurotransmitters (e.g. glutamate and y-aminobutyric acid) in addition to changes in oxygen utilization. The ability to measure these substances in the human brain is increasing our understanding of the pathophysiology of trauma, stroke, epilepsy and tumours. There are several techniques in clinical practice already in use and new methods are under evaluation. Such techniques include the use of cerebral probes (e.g. microdialysis. voltammetry and spectrophotometry) and functional imaging (e.g. positron emission tomography and magnetic resonance spectroscopy). This review describes these techniques in terms of their principles and clinical applications.
Collapse
Affiliation(s)
- P J Hutchinson
- Department of Neurosurgery and Wolfson Brain Imaging Centre, Addenbrooke's Hospital, University of Cambridge, UK.
| | | | | | | |
Collapse
|