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Wu T, Liu C, Thamizhchelvan AM, Fleischer C, Peng X, Liu G, Mao H. Label-Free Chemically and Molecularly Selective Magnetic Resonance Imaging. CHEMICAL & BIOMEDICAL IMAGING 2023; 1:121-139. [PMID: 37235188 PMCID: PMC10207347 DOI: 10.1021/cbmi.3c00019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/20/2023] [Accepted: 04/01/2023] [Indexed: 05/28/2023]
Abstract
Biomedical imaging, especially molecular imaging, has been a driving force in scientific discovery, technological innovation, and precision medicine in the past two decades. While substantial advances and discoveries in chemical biology have been made to develop molecular imaging probes and tracers, translating these exogenous agents to clinical application in precision medicine is a major challenge. Among the clinically accepted imaging modalities, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) exemplify the most effective and robust biomedical imaging tools. Both MRI and MRS enable a broad range of chemical, biological and clinical applications from determining molecular structures in biochemical analysis to imaging diagnosis and characterization of many diseases and image-guided interventions. Using chemical, biological, and nuclear magnetic resonance properties of specific endogenous metabolites and native MRI contrast-enhancing biomolecules, label-free molecular and cellular imaging with MRI can be achieved in biomedical research and clinical management of patients with various diseases. This review article outlines the chemical and biological bases of several label-free chemically and molecularly selective MRI and MRS methods that have been applied in imaging biomarker discovery, preclinical investigation, and image-guided clinical management. Examples are provided to demonstrate strategies for using endogenous probes to report the molecular, metabolic, physiological, and functional events and processes in living systems, including patients. Future perspectives on label-free molecular MRI and its challenges as well as potential solutions, including the use of rational design and engineered approaches to develop chemical and biological imaging probes to facilitate or combine with label-free molecular MRI, are discussed.
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Affiliation(s)
- Tianhe Wu
- Department
of Radiology and Imaging Sciences, Emory
University School of Medicine, Atlanta, Georgia 30322, United States
| | - Claire Liu
- F.M.
Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland 21205, United States
| | - Anbu Mozhi Thamizhchelvan
- Department
of Radiology and Imaging Sciences, Emory
University School of Medicine, Atlanta, Georgia 30322, United States
| | - Candace Fleischer
- Department
of Radiology and Imaging Sciences, Emory
University School of Medicine, Atlanta, Georgia 30322, United States
| | - Xingui Peng
- Jiangsu
Key Laboratory of Molecular and Functional Imaging, Department of
Radiology, Zhongda Hospital, Medical School
of Southeast University, Nanjing, Jiangsu 210009, China
| | - Guanshu Liu
- F.M.
Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland 21205, United States
- Russell
H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
| | - Hui Mao
- Department
of Radiology and Imaging Sciences, Emory
University School of Medicine, Atlanta, Georgia 30322, United States
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Santamaría G, Naude N, Bennett I, Vosburgh K, Ganau S, Bargalló X, Malycha P, Mountford C. In vivo assignment of methylmalonic acid in breast tissue using 2D MRS and relationship with breast density, menopausal status and cancer risk. NMR IN BIOMEDICINE 2023; 36:e4851. [PMID: 36259358 PMCID: PMC10078222 DOI: 10.1002/nbm.4851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 10/09/2022] [Accepted: 10/10/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Methylmalonic acid (MMA) is linked to progression and aggressiveness of tumours. A recent study showed that high levels of circulatory MMA directed genetic programs promoting cancer progression. PURPOSE To evaluate in vivo two-dimensional correlated spectroscopy (2D COSY) data from women at elevated risk of breast cancer to determine if resonances consistent with MMA are present, and if so to correlate levels with breast density, menopausal status and risk categories. MATERIALS AND METHODS With institutional review board approval, 106 women at elevated risk (mean age 47), including 46 participants at medium risk, 43 at high risk with no known mutation and 17 BRCA-mutation carriers, were recruited. Breast density was assessed using a T2 sequence. A T1 sequence was used to place the voxel for the 2D COSY data. Peak volumes were normalized to the methylene peak at (1.30, 1.30) ppm. Chi-squared and Mann-Whitney tests were used. RESULTS Two resonances are assigned on the diagonal at 3.15 ppm and 3.19 ppm consistent with and denoted MMA1 and MMA2 respectively. MMA1 and MMA2 increased in parallel with increased risk. BRCA-mutation carriers recorded an increase in mean MMA1 of 120% (p = 0.033) and MMA2 of 127% (p = 0.020) in comparison with participants with no known mutation. BRCA-mutation carriers with dense breasts recorded a significant increase in mean MMA1 of 137% (p = 0.002) and in mean MMA2 of 143% (p = 0.004) compared with BRCA-mutation participants with low-density breast tissue. MMA1 and MMA2 were higher in premenopausal women with dense breasts compared with those with low-density tissue. The highest values of MMA were recorded in BRCA-mutation carriers. CONCLUSION Two tentative assignments are made for MMA in breast tissue of women at elevated risk for cancer. BRCA-mutation carriers exhibited higher values of MMA than those with no known mutation. Premenopausal women with BRCA mutation and dense breasts recorded the highest levels of MMA compared with other categories.
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Affiliation(s)
- Gorane Santamaría
- Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
- Translational Research InstituteWoolloongabbaQueenslandAustralia
- School of Biomedical Sciences, Faculty of HealthQueensland University of TechnologyBrisbane CityQueenslandAustralia
| | - Natali Naude
- Translational Research InstituteWoolloongabbaQueenslandAustralia
- School of Biomedical Sciences, Faculty of HealthQueensland University of TechnologyBrisbane CityQueenslandAustralia
| | - Ian Bennett
- Department of Breast and Endocrine SurgeryPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
- Institute for Glycomics, Gold Coast CampusGriffith UniversitySouthportQueenslandAustralia
| | - Kirby Vosburgh
- Institute for Glycomics, Gold Coast CampusGriffith UniversitySouthportQueenslandAustralia
| | - Sergi Ganau
- Department of RadiologyHospital Clinic de BarcelonaBarcelonaSpain
| | - Xavier Bargalló
- Department of RadiologyHospital Clinic de BarcelonaBarcelonaSpain
| | - Peter Malycha
- Translational Research InstituteWoolloongabbaQueenslandAustralia
- Department of Breast and Endocrine SurgeryPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
- Institute for Glycomics, Gold Coast CampusGriffith UniversitySouthportQueenslandAustralia
| | - Carolyn Mountford
- Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
- Translational Research InstituteWoolloongabbaQueenslandAustralia
- Institute for Glycomics, Gold Coast CampusGriffith UniversitySouthportQueenslandAustralia
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Santamaría G, Naude N, Watson J, Irvine J, Lloyd T, Bennett I, Galloway G, Malycha P, Mountford C. Breast Tissue Chemistry Measured In Vivo In Healthy Women Correlate with Breast Density and Breast Cancer Risk. J Magn Reson Imaging 2022; 56:1355-1369. [PMID: 35319148 PMCID: PMC9790468 DOI: 10.1002/jmri.28168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The relationship of tissue chemistry to breast density and cancer risk has not been documented despite breast density being a known risk factor. PURPOSE To investigate whether distinct chemical profiles associated with breast density and cancer risk are identified in healthy breast tissue using in vivo two-dimensional correlated spectroscopy (2D COSY). STUDY TYPE Prospective. POPULATION One-hundred-seven participants including 55 at low risk and 52 at high risk of developing breast cancer. FIELD STRENGTH/SEQUENCE 3 T/ axial/ T1, T2, 2D COSY. ASSESSMENT Two radiologists defined breast density on T2. Interobserver variability assessed. Peak volumes normalized to methylene at (1.30, 1.30) ppm as internal shift reference. STATISTICAL TESTS Chi-squared/Mann-Whitney/Kappa statistics/Kruskal Wallis/pairwise analyses. Significance level 0.05. RESULTS Ten percentage were fatty breasts, 39% scattered fibroglandular, 35% heterogeneously dense, and 16% extremely dense. Interobserver variability was excellent (kappa = 0.817). Sixty percentage (64/107) were premenopausal. Four distinct tissue chemistry categories were identified: low-density (LD)/premenopausal, high-density (HD)/premenopausal, LD/postmenopausal, and HD/postmenopausal. Compared to LD, HD breast chemistry showed significant increases of cholesterol (235%) and lipid unsaturation (33%). In the low-risk category, postmenopausal women with dense breasts recorded the largest significant changes including cholesterol methyl 540%, lipid unsaturation 207%, glutamine/glutamate 900%, and choline/phosphocholine 800%. In the high-risk cohort, premenopausal women with HD recorded a more active chemical profile with significant increases in choline/phosphocholine 1100%, taurine/glucose 550% and cholesterol sterol 250%. DATA CONCLUSION Four distinct chemical profiles were identified in healthy breast tissue based on breast density and menopausal status in participants at low and high risk. Gradual increase in neutral lipid content and metabolites was noted in both risk groups across categories in different order. In low risk, the HD postmenopausal category exhibited the highest metabolic activity, while women at high risk exhibited the highest lipid content and metabolic activity in the HD premenopausal category. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 3.
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Affiliation(s)
- Gorane Santamaría
- Diagnostic ImagingTranslational Research InstituteWoolloongabbaQueenslandAustralia,Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Department of RadiologyHospital Clínic de BarcelonaBarcelonaSpain,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - Natali Naude
- Diagnostic ImagingTranslational Research InstituteWoolloongabbaQueenslandAustralia,Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - Julia Watson
- Diagnostic ImagingTranslational Research InstituteWoolloongabbaQueenslandAustralia,Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - John Irvine
- Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - Thomas Lloyd
- Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - Ian Bennett
- Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
| | - Graham Galloway
- Diagnostic ImagingTranslational Research InstituteWoolloongabbaQueenslandAustralia,Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - Peter Malycha
- Diagnostic ImagingTranslational Research InstituteWoolloongabbaQueenslandAustralia,Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia,Jones and Partners RadiologySt Andrew's HospitalAdelaideAustralia
| | - Carolyn Mountford
- Diagnostic ImagingTranslational Research InstituteWoolloongabbaQueenslandAustralia,Department of RadiologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Faculty of Health, Biomedical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
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Magnetic Resonance Imaging (MRI) and MR Spectroscopic Methods in Understanding Breast Cancer Biology and Metabolism. Metabolites 2022; 12:metabo12040295. [PMID: 35448482 PMCID: PMC9030399 DOI: 10.3390/metabo12040295] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 02/01/2023] Open
Abstract
A common malignancy that affects women is breast cancer. It is the second leading cause of cancer-related death among women. Metabolic reprogramming occurs during cancer growth, invasion, and metastases. Functional magnetic resonance (MR) methods comprising an array of techniques have shown potential for illustrating physiological and molecular processes changes before anatomical manifestations on conventional MR imaging. Among these, in vivo proton (1H) MR spectroscopy (MRS) is widely used for differentiating breast malignancy from benign diseases by measuring elevated choline-containing compounds. Further, the use of hyperpolarized 13C and 31P MRS enhanced the understanding of glucose and phospholipid metabolism. The metabolic profiling of an array of biological specimens (intact tissues, tissue extracts, and various biofluids such as blood, urine, nipple aspirates, and fine needle aspirates) can also be investigated through in vitro high-resolution NMR spectroscopy and high-resolution magic angle spectroscopy (HRMAS). Such studies can provide information on more metabolites than what is seen by in vivo MRS, thus providing a deeper insight into cancer biology and metabolism. The analysis of a large number of NMR spectral data sets through multivariate statistical methods classified the tumor sub-types. It showed enormous potential in the development of new therapeutic approaches. Recently, multiparametric MRI approaches were found to be helpful in elucidating the pathophysiology of cancer by quantifying structural, vasculature, diffusion, perfusion, and metabolic abnormalities in vivo. This review focuses on the applications of NMR, MRS, and MRI methods in understanding breast cancer biology and in the diagnosis and therapeutic monitoring of breast cancer.
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HR-MAS NMR Based Quantitative Metabolomics in Breast Cancer. Metabolites 2019; 9:metabo9020019. [PMID: 30678289 PMCID: PMC6410210 DOI: 10.3390/metabo9020019] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 01/17/2019] [Accepted: 01/18/2019] [Indexed: 01/23/2023] Open
Abstract
High resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy is increasingly used for profiling of breast cancer tissue, delivering quantitative information for approximately 40 metabolites. One unique advantage of the method is that it can be used to analyse intact tissue, thereby requiring only minimal sample preparation. Importantly, since the method is non-destructive, it allows further investigations of the same specimen using for instance transcriptomics. Here, we discuss technical aspects critical for a successful analysis—including sample handling, measurement conditions, pulse sequences for one- and two dimensional analysis, and quantification methods—and summarize available studies, with a focus on significant associations of metabolite levels with clinically relevant parameters.
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Di Leo G, Ioan I, Luciani ML, Midulla C, Podo F, Sardanelli F, Pediconi F. Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study. Eur Radiol Exp 2018; 2:43. [PMID: 30560497 PMCID: PMC6297122 DOI: 10.1186/s41747-018-0075-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 10/26/2018] [Indexed: 02/03/2023] Open
Abstract
Background To evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC). Methods After institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval. Results All spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3–2.4) on day 7, 0.9 (0.4–1.2) on day 14, and 0.4 (0.2–0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2–1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001). Conclusions A tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4–0.9 mM, constant over the MC and independent of OC use.
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Affiliation(s)
- Giovanni Di Leo
- Radiology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
| | - Ileana Ioan
- Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, Milan, Italy
| | - Maria Laura Luciani
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Cecilia Midulla
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Franca Podo
- Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy
| | - Francesco Sardanelli
- Radiology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy.,Department of Biomedical Sciences for Health, Università degli Studi di Milano, San Donato Milanese, Italy
| | - Federica Pediconi
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
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7
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Study of lipid metabolism by estimating the fat fraction in different breast tissues and in various breast tumor sub-types by in vivo 1H MR spectroscopy. Magn Reson Imaging 2018; 49:116-122. [PMID: 29454110 DOI: 10.1016/j.mri.2018.02.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 02/01/2018] [Accepted: 02/12/2018] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate the utility of fat fraction (FF) for the differentiation of different breast tissues and in various breast tumor subtypes using in vivo proton (1H) magnetic resonance spectroscopy (MRS). METHODS 1H MRS was performed on 68 malignant, 35 benign, and 30 healthy volunteers at 1.5 T. Malignant breast tissues of patients were characterized into different subtypes based on the differences in the expression of hormone receptors and the FF was calculated. Further, the sensitivity and specificity of FF to differentiate malignant from benign and from normal breast tissues of healthy volunteers was determined using receiver operator curve (ROC) analysis. RESULTS A significantly lower FF of malignant (median 0.12; range 0.01-0.70) compared to benign lesions (median 0.28; range 0.02-0.71) and normal breast tissue of healthy volunteers (median 0.39; range 0.06-0.76) was observed. No significant difference in FF was seen between benign lesions and normal breast tissues of healthy volunteers. Sensitivity and specificity of 75% and 68.6%, respectively was obtained to differentiate malignant from benign lesions. For the differentiation of malignant from healthy breast tissues, 76% sensitivity and 74.5% specificity was achieved. Higher FF was seen in patients with ER-/PR- status as compared to ER+/PR+ patients. Similarly, FF of HER2neu+ tumors were significantly higher than in HER2neu- breast tumors. CONCLUSION The results showed the potential of in vivo 1H MRS in providing insight into the changes in the fat content of different types of breast tissues and in various breast tumor subtypes.
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8
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Momcilovic M, Shackelford DB. Imaging Cancer Metabolism. Biomol Ther (Seoul) 2018; 26:81-92. [PMID: 29212309 PMCID: PMC5746040 DOI: 10.4062/biomolther.2017.220] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 11/11/2017] [Accepted: 11/13/2017] [Indexed: 12/23/2022] Open
Abstract
It is widely accepted that altered metabolism contributes to cancer growth and has been described as a hallmark of cancer. Our view and understanding of cancer metabolism has expanded at a rapid pace, however, there remains a need to study metabolic dependencies of human cancer in vivo. Recent studies have sought to utilize multi-modality imaging (MMI) techniques in order to build a more detailed and comprehensive understanding of cancer metabolism. MMI combines several in vivo techniques that can provide complementary information related to cancer metabolism. We describe several non-invasive imaging techniques that provide both anatomical and functional information related to tumor metabolism. These imaging modalities include: positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) that uses hyperpolarized probes and optical imaging utilizing bioluminescence and quantification of light emitted. We describe how these imaging modalities can be combined with mass spectrometry and quantitative immunochemistry to obtain more complete picture of cancer metabolism. In vivo studies of tumor metabolism are emerging in the field and represent an important component to our understanding of how metabolism shapes and defines cancer initiation, progression and response to treatment. In this review we describe in vivo based studies of cancer metabolism that have taken advantage of MMI in both pre-clinical and clinical studies. MMI promises to advance our understanding of cancer metabolism in both basic research and clinical settings with the ultimate goal of improving detection, diagnosis and treatment of cancer patients.
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Affiliation(s)
- Milica Momcilovic
- Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, Los Angeles, CA, 90095, USA
| | - David B Shackelford
- Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, Los Angeles, CA, 90095, USA
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Shelton SE, Lindsey BD, Dayton PA, Lee YZ. First-in-Human Study of Acoustic Angiography in the Breast and Peripheral Vasculature. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:2939-2946. [PMID: 28982628 PMCID: PMC6267932 DOI: 10.1016/j.ultrasmedbio.2017.08.1881] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 08/20/2017] [Accepted: 08/21/2017] [Indexed: 05/07/2023]
Abstract
Screening with mammography has been found to increase breast cancer survival rates by about 20%. However, the current system in which mammography is used to direct patients toward biopsy or surgical excision also results in relatively high rates of unnecessary biopsy, as 66.8% of biopsies are benign. A non-ionizing radiation imaging approach with increased specificity might reduce the rate of unnecessary biopsies. Quantifying the vascular characteristics within and surrounding lesions represents one potential target for assessing likelihood of malignancy via imaging. In this clinical note, we describe the translation of a contrast-enhanced ultrasound technique, acoustic angiography, to human imaging. We illustrate the feasibility of this technique with initial studies in imaging the hand, wrist and breast using Definity microbubble contrast agent and a mechanically steered prototype dual-frequency transducer in healthy volunteers. Finally, this approach was used to image pre-biopsy Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 lesions <2 cm in depth in 11 patients. Results indicate that sensitivity and spatial resolution are sufficient to image vessels as small as 0.2 mm in diameter at depths of ~15 mm in the human breast. Challenges observed include motion artifacts, as well as limited depth of field and sensitivity, which could be improved by correction algorithms and improved transducer technologies.
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Affiliation(s)
- Sarah E Shelton
- Joint Department of Biomedical Engineering, University of North Carolina-Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA
| | - Brooks D Lindsey
- Joint Department of Biomedical Engineering, University of North Carolina-Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA
| | - Paul A Dayton
- Joint Department of Biomedical Engineering, University of North Carolina-Chapel Hill and North Carolina State University, Raleigh, North Carolina, USA; Biomedical Research Imaging Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
| | - Yueh Z Lee
- Biomedical Research Imaging Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA; Department of Radiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA
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10
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Clauser P, Marcon M, Dietzel M, Baltzer PA. A new method to reduce false positive results in breast MRI by evaluation of multiple spectral regions in proton MR-spectroscopy. Eur J Radiol 2017. [DOI: 10.1016/j.ejrad.2017.04.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Palma A, Grande S, Luciani AM, Mlynárik V, Guidoni L, Viti V, Rosi A. Metabolic Study of Breast MCF-7 Tumor Spheroids after Gamma Irradiation by (1)H NMR Spectroscopy and Microimaging. Front Oncol 2016; 6:105. [PMID: 27200293 PMCID: PMC4848320 DOI: 10.3389/fonc.2016.00105] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 04/13/2016] [Indexed: 12/14/2022] Open
Abstract
Multicellular tumor spheroids are an important model system to investigate the response of tumor cells to radio- and chemotherapy. They share more properties with the original tumor than cells cultured as 2D monolayers do, which helps distinguish the intrinsic properties of monolayer cells from those induced during cell aggregation in 3D spheroids. The paper investigates some metabolic aspects of small tumor spheroids of breast cancer and their originating MCF-7 cells, grown as monolayer, by means of high-resolution (HR) (1)H NMR spectroscopy and MR microimaging before and after gamma irradiation. The spectra of spheroids were characterized by higher intensity of mobile lipids, mostly neutral lipids, and glutamine (Gln) signals with respect to their monolayer cells counterpart, mainly owing to the lower oxygen supply in spheroids. Morphological changes of small spheroids after gamma-ray irradiation, such as loss of their regular shape, were observed by MR microimaging. Lipid signal intensity increased after irradiation, as evidenced in both MR localized spectra of the single spheroid and in HR NMR spectra of spheroid suspensions. Furthermore, the intense Gln signal from spectra of irradiated spheroids remained unchanged, while the low Gln signal observed in monolayer cells increased after irradiation. Similar results were observed in cells grown in hypoxic conditions. The different behavior of Gln in 2D monolayers and in 3D spheroids supports the hypothesis that a lower oxygen supply induces both an upregulation of Gln synthetase and a downregulation of glutaminases with the consequent increase in Gln content, as already observed under hypoxic conditions. The data herein indicate that (1)H NMR spectroscopy can be a useful tool for monitoring cell response to different constraints. The use of spheroid suspensions seems to be a feasible alternative to localized spectroscopy since similar effects were found after radiation treatment.
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Affiliation(s)
- Alessandra Palma
- Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy; INFN Sezione di Roma, Rome, Italy
| | - Sveva Grande
- Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy; INFN Sezione di Roma, Rome, Italy
| | - Anna Maria Luciani
- Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy; INFN Sezione di Roma, Rome, Italy
| | - Vladimír Mlynárik
- Department of Biomedical Imaging and Image-Guided Therapy, High-Field MR Center, Medical University of Vienna , Vienna , Austria
| | | | | | - Antonella Rosi
- Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy; INFN Sezione di Roma, Rome, Italy
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Telegrafo M, Rella L, Stabile Ianora AA, Angelelli G, Moschetta M. Unenhanced breast MRI (STIR, T2-weighted TSE, DWIBS): An accurate and alternative strategy for detecting and differentiating breast lesions. Magn Reson Imaging 2015; 33:951-5. [DOI: 10.1016/j.mri.2015.06.002] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Revised: 05/04/2015] [Accepted: 06/20/2015] [Indexed: 10/23/2022]
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Cen D, Xu L. Differential diagnosis between malignant and benign breast lesions using single-voxel proton MRS: a meta-analysis. J Cancer Res Clin Oncol 2014; 140:993-1001. [PMID: 24595596 DOI: 10.1007/s00432-014-1605-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Accepted: 01/30/2014] [Indexed: 12/26/2022]
Abstract
OBJECTIVES We aim to investigate the diagnostic capability of single-voxel proton MR spectroscopy (MRS) for benign/malignant discrimination of focal breast lesions with a meta-analysis. MATERIALS AND METHODS The meta-analysis included a total of 750 malignant breast lesions and 419 benign breast lesions from eighteen studies. RESULTS The pooled sensitivity and specificity of MRS were 0.71 (95 % CI 0.68-0.74) and 0.85 (95 % CI 0.81-0.88), respectively. The positive likelihood ratio and negative LR were 4.11 (95 % CI 3.11-5.43) and 0.25 (95 % CI 0.17-0.36), respectively. The P value for χ(2) heterogeneity for all pooled estimates was <0.05. From the fitted summary receiver operating characteristics curve, AUC was 0.89 and Q* was 0.84. Asymmetrical in funnel plots indicated there may be publication bias (t = 2.85, P = 0.012). The meta-regression analysis indicated that neither threshold effect nor evaluated covariates that include strength of field, scanning technique (PRESS or STEAM), repetition time, NSA, and pre- or post-contrast agent were the sources of heterogeneity (all P value >0.05). CONCLUSIONS Single-voxel proton MRS was useful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated. The standardization of the acquisition protocol for MRS across the multicenter trials is recommended.
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Affiliation(s)
- Dongzhi Cen
- Department of Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong Province, People's Republic of China
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Menezes GLG, Knuttel FM, Stehouwer BL, Pijnappel RM, van den Bosch MAAJ. Magnetic resonance imaging in breast cancer: A literature review and future perspectives. World J Clin Oncol 2014; 5:61-70. [PMID: 24829852 PMCID: PMC4014797 DOI: 10.5306/wjco.v5.i2.61] [Citation(s) in RCA: 100] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 03/18/2014] [Accepted: 04/17/2014] [Indexed: 02/06/2023] Open
Abstract
Early detection and diagnosis of breast cancer are essential for successful treatment. Currently mammography and ultrasound are the basic imaging techniques for the detection and localization of breast tumors. The low sensitivity and specificity of these imaging tools resulted in a demand for new imaging modalities and breast magnetic resonance imaging (MRI) has become increasingly important in the detection and delineation of breast cancer in daily practice. However, the clinical benefits of the use of pre-operative MRI in women with newly diagnosed breast cancer is still a matter of debate. The main additional diagnostic value of MRI relies on specific situations such as detecting multifocal, multicentric or contralateral disease unrecognized on conventional assessment (particularly in patients diagnosed with invasive lobular carcinoma), assessing the response to neoadjuvant chemotherapy, detection of cancer in dense breast tissue, recognition of an occult primary breast cancer in patients presenting with cancer metastasis in axillary lymph nodes, among others. Nevertheless, the development of new MRI technologies such as diffusion-weighted imaging, proton spectroscopy and higher field strength 7.0 T imaging offer a new perspective in providing additional information in breast abnormalities. We conducted an expert literature review on the value of breast MRI in diagnosing and staging breast cancer, as well as the future potentials of new MRI technologies.
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Lynch K, O'Brien R. ¹H magnetic resonance spectroscopy: a review of the current literature and its potential utility in veterinary oncology. Vet J 2014; 200:240-7. [PMID: 24662026 DOI: 10.1016/j.tvjl.2014.02.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Revised: 02/04/2014] [Accepted: 02/06/2014] [Indexed: 11/15/2022]
Abstract
Advanced imaging of veterinary cancer patients has evolved in recent years and modalities once limited to human medicine have now been described for diagnostic purposes in veterinary medicine (positron emission tomography/computed tomography, single-photon emission computed tomography, whole body magnetic resonance imaging). Magnetic resonance spectroscopy (MRS) is a non-invasive and non-ionizing technique that is well described in the human medical literature and is most frequently used to evaluate the metabolic activity of tissues with questionable malignant transformation. Differentiation of neoplastic tissue from surrounding normal tissue is dependent on variations in cellular metabolism. Positive identification of malignancy can be made when neoplastic alterations are occurring at the cellular level prior to gross anatomic changes. This improved, early detection of cancer occurrence (or recurrence) can improve patient survival and direct medical therapy. MRS techniques are largely underutilized in veterinary medicine, with current research predominantly limited to the brain (both evaluation of normal and diseased tissue). Given the clinical utility of MRS in humans, the technique may also be useful in the staging of cancer in veterinary medicine.
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Affiliation(s)
- Katherine Lynch
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801, USA.
| | - Robert O'Brien
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801, USA
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Tsougos I, Svolos P, Kousi E, Athanassiou E, Theodorou K, Arvanitis D, Fezoulidis I, Vassiou K. The contribution of diffusion tensor imaging and magnetic resonance spectroscopy for the differentiation of breast lesions at 3T. Acta Radiol 2014; 55:14-23. [PMID: 23864060 DOI: 10.1177/0284185113492152] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Conventional breast magnetic resonance imaging (MRI), including dynamic contrast-enhanced MR mammography (DCE-MRM), may lead to ambiguous diagnosis and unnecessary biopsies. PURPOSE To investigate the contribution of proton MR spectroscopy (1H-MRS) combined with diffusion tensor imaging (DTI) metrics in the discrimination between benign and malignant breast lesions. MATERIAL AND METHODS Fifty-one women with known breast abnormalities from conventional imaging were examined on a 3T MR scanner. DTI was performed during breast MRI, and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in the breast lesions and the contralateral normal breast. FA and ADC were compared between malignant lesions, benign lesions, and normal tissue. 1H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. RESULTS In our study 1H-MRS showed a sensitivity of 93.5%, specificity 80%, and accuracy 88.2%. FA was significantly higher in breast carcinomas compared to benign lesions. However, no significant difference was observed in ADC between benign and malignant lesions. The combination of Cho presence and FA achieved higher levels of accuracy and specificity in discriminating malignant from benign lesions over Cho presence or FA alone. CONCLUSION In conclusion, applying DTI and 1H-MRS together, adds incremental diagnostic value in the characterization of breast lesions and may sufficiently improve the low specificity of conventional breast MRI.
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Affiliation(s)
- Ioannis Tsougos
- Department of Medical Physics, University of Thessaly Medical School, Larissa, Greece
| | - Patricia Svolos
- Department of Medical Physics, University of Thessaly Medical School, Larissa, Greece
| | - Evanthia Kousi
- Department of Medical Physics, University of Thessaly Medical School, Larissa, Greece
| | | | - Kiriaki Theodorou
- Department of Medical Physics, University of Thessaly Medical School, Larissa, Greece
| | - Dimitrios Arvanitis
- Department of Anatomy-Histology-Embryology, University of Thessaly Medical School, Larissa, Greece
| | - Ioannis Fezoulidis
- Department of Diagnostic Radiology, University of Thessaly Medical School, Larissa, Greece
| | - Katerina Vassiou
- Department of Diagnostic Radiology, University of Thessaly Medical School, Larissa, Greece
- Department of Anatomy-Histology-Embryology, University of Thessaly Medical School, Larissa, Greece
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MR-spectroscopy at 1.5 tesla and 3 tesla. Useful? A systematic review and meta-analysis. Eur J Radiol 2013; 81 Suppl 1:S6-9. [PMID: 23083604 DOI: 10.1016/s0720-048x(12)70003-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Baltzer PAT, Dietzel M. Breast Lesions: Diagnosis by Using Proton MR Spectroscopy at 1.5 and 3.0 T—Systematic Review and Meta-Analysis. Radiology 2013; 267:735-46. [DOI: 10.1148/radiol.13121856] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Vassiou K, Tsougos I, Kousi E, Vlychou M, Athanasiou E, Theodorou K, Arvanitis DL, Fezoulidis IV. Application value of 3T ¹H-magnetic resonance spectroscopy in diagnosing breast tumors. Acta Radiol 2013; 54:380-8. [PMID: 23436823 DOI: 10.1177/0284185113475921] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Assessment of breast lesions with magnetic resonance imaging (MRI) provides a means for lesion detection and diagnosis. Proton (hydrogen-1) magnetic resonance spectroscopy ((1)H-MRS) has been proposed as a useful diagnostic technique in providing metabolic information of suspicious breast lesions. PURPOSE To determine the clinical significance of in-vivo single voxel (1)H-MRS at 3T in the assessment of benign and malignant breast lesions in combination with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIAL AND METHODS Twenty-four women with known breast abnormalities from conventional imaging (mammography, ultrasonography) underwent DCE-MRI at a 3T MR scanner and 26 breast lesions were detected. Breast lesions were assessed according BI-RADS classification. Single voxel (1)H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. All lesions were confirmed histologically from the surgically excised specimens. Sensitivity, specificity, and accuracy of the (1)H-MRS, of the BI-RADS classification and of their combination (DCE-MRI + (1)H-MRS) were calculated. RESULTS Fifteen out of 26 lesions proved to be malignant and 11 proved to be benign. In our study (1)H-MRS showed sensitivity 80%, specificity 81.8%, and accuracy 80.7%. DCE-MRI showed sensitivity 100%, specificity 63.6%, and accuracy 84.6%. The combination of DCE-MRI and (1)H-MRS provided higher accuracy (96.4%), as well as higher specificity 81.8% compared to BI-RADS classification. CONCLUSION The combined use of (1)H-MRS and DCE-MRI found to have improved diagnostic performance in the assessment of equivocal breast lesions. (1)H-MRS can be used as a useful adjunct during lesion characterization in clinical routine in cases classified as BI-RADS 3 and 4.
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Abdel Razek AAK, Poptani H. MR spectroscopy of head and neck cancer. Eur J Radiol 2013; 82:982-9. [PMID: 23485098 DOI: 10.1016/j.ejrad.2013.01.025] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 01/17/2013] [Accepted: 01/19/2013] [Indexed: 12/16/2022]
Abstract
The aim of this review is to discuss the technique and potential applications of magnetic resonance spectroscopy (MRS) in head and neck cancer. We illustrate the technical issues related to data acquisition, post processing and interpretation of MRS of head and neck lesions. MRS has been used for differentiation of squamous cell carcinoma from normal tissue. The main potential clinical application of proton MRS ((1)H-MRS) is monitoring patients with head and neck cancer undergoing therapy. Pretreatment prediction of response to therapy can be done with phosphorus MRS ((31)P-MRS). Although performance of MRS of head and neck is challenging, technological advances in both software and hardware has the potential to impact on the clinical management of patients with head and neck cancer.
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L-COSY of breast cancer at 3T. Eur J Radiol 2012; 81 Suppl 1:S129-31. [DOI: 10.1016/s0720-048x(12)70053-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Zhao C, Bolan PJ, Royce M, Lakkadi N, Eberhardt S, Sillerud L, Lee SJ, Posse S. Quantitative mapping of total choline in healthy human breast using proton echo planar spectroscopic imaging (PEPSI) at 3 Tesla. J Magn Reson Imaging 2012; 36:1113-23. [PMID: 22782667 DOI: 10.1002/jmri.23748] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2011] [Accepted: 06/01/2012] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To quantitatively measure tCho levels in healthy breasts using Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI). MATERIALS AND METHODS The two-dimensional mapping of tCho at 3 Tesla across an entire breast slice using PEPSI and a hybrid spectral quantification method based on LCModel fitting and integration of tCho using the fitted spectrum were developed. This method was validated in 19 healthy females and compared with single voxel spectroscopy (SVS) and with PRESS prelocalized conventional Magnetic Resonance Spectroscopic Imaging (MRSI) using identical voxel size (8 cc) and similar scan times (∼7 min). RESULTS A tCho peak with a signal to noise ratio larger than 2 was detected in 10 subjects using both PEPSI and SVS. The average tCho concentration in these subjects was 0.45 ± 0.2 mmol/kg using PEPSI and 0.48 ± 0.3 mmol/kg using SVS. Comparable results were obtained in two subjects using conventional MRSI. High lipid content in the spectra of nine tCho negative subjects was associated with spectral line broadening of more than 26 Hz, which made tCho detection impossible. Conventional MRSI with PRESS prelocalization in glandular tissue in two of these subjects yielded tCho concentrations comparable to PEPSI. CONCLUSION The detection sensitivity of PEPSI is comparable to SVS and conventional PRESS-MRSI. PEPSI can be potentially used in the evaluation of tCho in breast cancer. A tCho threshold concentration value of ∼0.7 mmol/kg might be used to differentiate between cancerous and healthy (or benign) breast tissues based on this work and previous studies.
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Affiliation(s)
- Chenguang Zhao
- Department of Neurology and UNM Cancer Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
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Kousi E, Tsougos I, Vasiou K, Theodorou K, Poultsidi A, Fezoulidis I, Kappas C. Magnetic resonance spectroscopy of the breast at 3T: pre- and post-contrast evaluation for breast lesion characterization. ScientificWorldJournal 2012; 2012:754380. [PMID: 22645448 PMCID: PMC3356737 DOI: 10.1100/2012/754380] [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: 11/23/2011] [Accepted: 12/25/2011] [Indexed: 01/13/2023] Open
Abstract
PURPOSE To determine whether in vivo proton magnetic resonance spectroscopy at 3T can provide accurate breast lesion characterization, and to determine the effect of gadolinium on the resonance of tCho. METHODS Twenty-four positive-mammogram patients were examined on a 3T MR scanner. 1H-MRS was performed before and after gadolinium administration. tCho peak was qualitatively evaluated before and after contrast injection. RESULTS Fourteen out of 27 lesions proved to be malignant after histopathological diagnosis. Using 1H-MRS, before contrast injection, 6/14 confirmed malignancies and 11/13 benign lesions were correctly classified; while, after contrast injection, 11/14 confirmed malignancies and 12/13 benign processes were correctly classified. Post gadolinium 1H-MRS proved useful in picking up tCho signal, improving the overall accuracy, sensitivity, and specificity by 35%, 83%, and 9%, respectively. CONCLUSION 1H-MRS overall accuracy, sensitivity, and specificity in detecting breast lesion's malignancy were increased after gadolinium administration. It is prudent to perform 1H-MRS before contrast injection in large breast lesions to avoid choline underestimation. In cases of small or non-mass lesions, it is recommended to perform 1H-MRS after contrast injection for better voxel prescription to enable a reliable preoperative diagnosis.
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Affiliation(s)
- E Kousi
- Medical Physics Department, University of Thessaly, Biopolis, 41110 Larissa, Greece
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Baltzer PAT, Gussew A, Dietzel M, Rzanny R, Gajda M, Camara O, Reichenbach JR, Kaiser WA. Effect of contrast agent on the results of in vivo ¹H MRS of breast tumors - is it clinically significant? NMR IN BIOMEDICINE 2012; 25:67-74. [PMID: 21557368 DOI: 10.1002/nbm.1714] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2010] [Revised: 02/16/2011] [Accepted: 02/17/2011] [Indexed: 05/30/2023]
Abstract
Choline (Cho) signal identification and quantification in (1)H MRS are used in breast cancer diagnosis. However, an influence of the gadolinium-based contrast agent on the Cho amplitude has been reported experimentally. This study aims to identify the impact of gadolinium-based contrast agents on Cho detection and quantification in postcontrast breast MRS. Consecutive patients were recruited prospectively and randomly allocated to two groups. Group A received a neutral (gadolinium diethylenetriaminepentaacetic acid bis-methylamide) and group B an ionic (gadolinium diethylenetriaminepentaacetic acid) contrast agent, each at a dosage of 0.1 mmol/kg. First, the presence of Cho was identified visually. Then, the normalized Cho intensity in malignant lesions was quantified. Multivariate analysis was applied to identify independent influencing factors on Cho. Sixty-three lesions were investigated [A, n = 34; B, n = 29; 43 malignant (one bilaterally malignant), 20 benign]. Cho was identified visually in 14 of 20 malignant tumors in group A and 12 of 22 malignant tumors in group B (p = 0.477). Normalized Cho differed significantly (p = 0.001) between groups A (mean, 26.8 ± 6.0 AU) and B (mean, 18.2 ± 12.5 AU). No linewidth differences were identified (p > 0.05). Multivariate analysis revealed only group membership (A versus B) as an independent predictor of Cho (p = 0.017). The results suggest stronger negative effects of an ionic relative to a neutral gadolinium-based contrast agent on breast tumor MRS in vivo. These results should be considered when conducting and comparing quantitative Cho measurements in the breast.
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Affiliation(s)
- Pascal A T Baltzer
- Institute of Diagnostic and Interventional Radiology, Friedrich Schiller University Jena, Germany.
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25
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Palma A, Grande S, Rosi A, Luciani AM, Guidoni L, Viti V. (1)H-MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line. NMR IN BIOMEDICINE 2011; 24:1099-1110. [PMID: 21290459 DOI: 10.1002/nbm.1665] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2010] [Revised: 10/22/2010] [Accepted: 12/07/2010] [Indexed: 05/30/2023]
Abstract
Glycosylation is the most abundant and diverse form of post-translational modification of proteins. Two types of glycans exist in glycoproteins: N-glycans and O-glycans often coexisting in the same protein. O-glycosylation is frequently found on secreted or membrane-bound mucins whose overexpression and structure alterations are associated with many types of cancer. Mucins have several cancer-associated structures, including high levels of Lewis antigens characterized by the presence of terminal fucose. The present study deals with the identification of MR signals from N-acetylgalactosamine and from fucose in HeLa cells by detecting a low-field signal in one-dimensional (1D) spectra assigned to the NH of N-acetylgalactosamine and some cross peaks assigned to fucose in two-dimensional (2D) spectra. The increase of Golgi pH by treatment with ammonium chloride allowed the N-acetylgalactosamine signal assignment to be confirmed. Behaviour of MR peak during cell growth and comparison with studies from literature taken together made it possible to have more insight into the relationship between aberrantly processed mucin and the presence of non-processed N-acetylgalactosamine residues in HeLa cells. Fucose signals, tentatively ascribed to residues bound to galactose and to N-acetylglucosamine, are visible in both intact cell and perchloric acid spectra. Signals assigned to fucose bound to galactose are more evident in ammonium chloride-treated cells where structural changes of mucin-related Lewis antigens are expected as a result of the higher Golgi pH. A common origin for the N-acetylgalactosamine and fucose resonances attributing them to aberrantly processed mucin can be inferred from the present results.
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Affiliation(s)
- Alessandra Palma
- Dipartimento di Tecnologie e Salute and INFN Gruppo Collegato Sanità, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy
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Fusion of dynamic contrast-enhanced magnetic resonance mammography at 3.0T with X-ray mammograms: Pilot study evaluation using dedicated semi-automatic registration software. Eur J Radiol 2011; 79:e98-e102. [DOI: 10.1016/j.ejrad.2011.04.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Accepted: 04/06/2011] [Indexed: 11/24/2022]
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Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia 2011; 13:81-97. [PMID: 21403835 DOI: 10.1593/neo.101102] [Citation(s) in RCA: 568] [Impact Index Per Article: 40.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2010] [Revised: 10/18/2010] [Accepted: 10/22/2010] [Indexed: 12/13/2022] Open
Abstract
A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as (13)C or (15)N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism-poor sensitivity-while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care.
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Patel GS, Kiuchi T, Lawler K, Ofo E, Fruhwirth GO, Kelleher M, Shamil E, Zhang R, Selvin PR, Santis G, Spicer J, Woodman N, Gillett CE, Barber PR, Vojnovic B, Kéri G, Schaeffter T, Goh V, O'Doherty MJ, Ellis PA, Ng T. The challenges of integrating molecular imaging into the optimization of cancer therapy. Integr Biol (Camb) 2011; 3:603-31. [PMID: 21541433 DOI: 10.1039/c0ib00131g] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
We review novel, in vivo and tissue-based imaging technologies that monitor and optimize cancer therapeutics. Recent advances in cancer treatment centre around the development of targeted therapies and personalisation of treatment regimes to individual tumour characteristics. However, clinical outcomes have not improved as expected. Further development of the use of molecular imaging to predict or assess treatment response must address spatial heterogeneity of cancer within the body. A combination of different imaging modalities should be used to relate the effect of the drug to dosing regimen or effective drug concentration at the local site of action. Molecular imaging provides a functional and dynamic read-out of cancer therapeutics, from nanometre to whole body scale. At the whole body scale, an increase in the sensitivity and specificity of the imaging probe is required to localise (micro)metastatic foci and/or residual disease that are currently below the limit of detection. The use of image-guided endoscopic biopsy can produce tumour cells or tissues for nanoscopic analysis in a relatively patient-compliant manner, thereby linking clinical imaging to a more precise assessment of molecular mechanisms. This multimodality imaging approach (in combination with genetics/genomic information) could be used to bridge the gap between our knowledge of mechanisms underlying the processes of metastasis, tumour dormancy and routine clinical practice. Treatment regimes could therefore be individually tailored both at diagnosis and throughout treatment, through monitoring of drug pharmacodynamics providing an early read-out of response or resistance.
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Affiliation(s)
- G S Patel
- Richard Dimbleby Department of Cancer Research, Randall Division & Division of Cancer Studies, King's College London, Guy's Medical School Campus, London, SE1 1UL, UK.
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Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy. JOURNAL OF ONCOLOGY 2011; 2011:174019. [PMID: 21577256 PMCID: PMC3090613 DOI: 10.1155/2011/174019] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Revised: 02/03/2011] [Accepted: 02/28/2011] [Indexed: 11/17/2022]
Abstract
Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using (1)H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.
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Muralidhar GS, Bovik AC, Sampat MP, Whitman GJ, Haygood TM, Stephens TW, Markey MK. Computer-Aided Diagnosis in Breast Magnetic Resonance Imaging. ACTA ACUST UNITED AC 2011; 78:280-90. [DOI: 10.1002/msj.20248] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Dietzel M, Baltzer PAT, Vag T, Herzog A, Gajda M, Camara O, Kaiser WA. The necrosis sign in magnetic resonance-mammography: diagnostic accuracy in 1,084 histologically verified breast lesions. Breast J 2011; 16:603-8. [PMID: 21070437 DOI: 10.1111/j.1524-4741.2010.00982.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Necrosis sign (NS) is a new descriptor for differential diagnosis of breast lesions in magnetic resonance (MR)-mammography (MRM). This study was designed: (a) to analyze diagnostic accuracy of NS in 1,084 histologically verified breast lesions, (b) to assess performance of NS in subgroups. This study was approved by the local ethical committee. All histologically verified lesions having undergone MR-mammography at our institution over 12 years were evaluated by experienced radiologists (> 500 MRM) according to standard protocols and study design (T1w; 0.1 mmol/kg bw gadolinium diethylenetriamine penta-acetic acid; T2-turbo spin echo (TSE)). Patients with history of breast biopsy (surgically, minimal-invasive), radiation- or chemotherapy ≤ 1 year before MRM were excluded. NS was assessed on T2w-TSE sequences and was rated positive if a hyperintense center in a hypointense lesion could be visualized (chi-squared test). One thousand and eighty-four lesions were available for statistical analysis (648: malignant, 436: benign). NS was significantly associated with malignancy (p < 0.001), providing specificity and positive predictive value (PPV) of 96.1% and 78.8%. Malignant lesions > 20 mm presented significantly more often NS (p < 0.001) than neoplasias ≤ 20 mm. There was no difference regarding prevalence of NS in small versus advanced benign lesions (n.s.), leading to better performance of NS in lesions > 20 mm (PPV: 87.8%). Correlation between NS and Grading of invasive carcinomas was significant. In this study of 1,084 lesions necrosis sign was a specific and highly predictive feature for differential diagnosis in MRM (Specificity: 96.1%; PPV: 78.8%). This particularly counts for advanced lesions (PPV 87.8%). As this new descriptor correlates with Grading, it could be used as an initial estimate of patient's prognosis.
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Affiliation(s)
- Matthias Dietzel
- Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Germany.
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Robert O, Sabatier J, Desoubzdanne D, Lalande J, Balayssac S, Gilard V, Martino R, Malet-Martino M. pH optimization for a reliable quantification of brain tumor cell and tissue extracts with (1)H NMR: focus on choline-containing compounds and taurine. Anal Bioanal Chem 2010; 399:987-99. [PMID: 21069302 DOI: 10.1007/s00216-010-4321-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Revised: 10/03/2010] [Accepted: 10/10/2010] [Indexed: 12/23/2022]
Abstract
The aim of this study was to define the optimal pH for (1)H nuclear magnetic resonance (NMR) spectroscopy analysis of perchloric acid or methanol-chloroform-water extracts from brain tumor cells and tissues. The systematic study of the proton chemical shift variations as a function of pH of 13 brain metabolites in model solutions demonstrated that recording (1)H NMR spectra at pH 10 allowed resolving resonances that are overlapped at pH 7, especially in the 3.2-3.3 ppm choline-containing-compounds region. (1)H NMR analysis of extracts at pH 7 or 10 showed that quantitative measurements of lactate, alanine, glutamate, glutamine (Gln), creatine + phosphocreatine and myo-inositol (m-Ino) can be readily performed at both pHs. The concentrations of glycerophosphocholine, phosphocholine and choline that are crucial metabolites for tumor brain malignancy grading were accurately measured at pH 10 only. Indeed, the resonances of their trimethylammonium moieties are cleared of any overlapping signal, especially those of taurine (Tau) and phosphoethanolamine. The four non-ionizable Tau protons resonating as a singlet in a non-congested spectral region permits an easier and more accurate quantitation of this apoptosis marker at pH 10 than at pH 7 where the triplet at 3.43 ppm can be overlapped with the signals of glucose or have an intensity too low to be measured. Glycine concentration was determined indirectly at both pHs after subtracting the contribution of the overlapped signals of m-Ino at pH 7 or Gln at pH 10.
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Affiliation(s)
- O Robert
- UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Groupe de RMN Biomédicale, Université de Toulouse, 118 route de Narbonne, 31062, Toulouse, Cedex 9, France
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Bohndiek SE, Brindle KM. Imaging and 'omic' methods for the molecular diagnosis of cancer. Expert Rev Mol Diagn 2010; 10:417-34. [PMID: 20465497 DOI: 10.1586/erm.10.20] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Molecular imaging methods can noninvasively detect specific biological processes that are aberrant in cancer, including upregulated glycolytic metabolism, increased cellular proliferation and altered receptor expression. PET using the glucose analogue 18F-fluoro-2-deoxyglucose, which detects the increased glucose uptake that is a characteristic of tumor cells, has been widely used in the clinic to detect tumors and their responses to treatment; however, there are many new PET tracers being developed for a wide range of biological targets. Magnetic resonance spectroscopy (MRS), which can be used to detect cellular metabolites, can also provide prognostic information, particularly in brain, breast and prostate cancers. An emerging technique, which by hyperpolarizing 13C-labeled cell substrates dramatically enhances their sensitivity to detection, could further extend the use of MRS in molecular imaging in the clinic. Molecular diagnostics applied to serum samples or tumor samples obtained by biopsy, can measure changes at the individual cell level and the underlying changes in gene or protein expression. DNA microarrays enable high-throughput gene-expression profiling, while mass spectrometry can detect thousands of proteins that may be used in the future as biomarkers of cancer. Probing molecular changes will aid not only cancer diagnosis, but also provide tumor grading, based on gene-expression analysis and imaging measurements of cell proliferation and changes in metabolism; staging, based on imaging of metastatic spread and elevation of protein biomarkers; and the detection of therapeutic response, using serial molecular imaging measurements or monitoring of serum markers. The present article provides a summary of the molecular diagnostic methods that are currently being trialed in the clinic.
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Affiliation(s)
- Sarah E Bohndiek
- Department of Biochemistry, University of Cambridge and Cancer Research UK Cambridge Research Institute, Cambridge, UK
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Baltzer PAT, Schäfer A, Dietzel M, Grässel D, Gajda M, Camara O, Kaiser WA. Diffusion tensor magnetic resonance imaging of the breast: a pilot study. Eur Radiol 2010; 21:1-10. [PMID: 20668860 DOI: 10.1007/s00330-010-1901-9] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2010] [Revised: 06/13/2010] [Accepted: 07/10/2010] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Diffusion-weighted MR imaging has shown diagnostic value for differential diagnosis of breast lesions. Diffusion tensor imaging (DTI) adds information about tissue microstructure by addressing diffusion direction. We have examined the diagnostic application of DTI of the breast. METHODS A total of 59 patients (71 lesions: 54 malignant, 17 benign) successfully underwent prospective echo planar imaging-DTI (EPI-DTI) (1.5 T). First, diffusion direction both of parenchyma as well as lesions was assessed on parametric maps. Subsequently, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured. Statistics included univariate (Mann-Whitney U test, receiver operating analysis) and multivariate (logistic regression analysis, LRA) tests. RESULTS Main diffusion direction of parenchyma was anterior-posterior in the majority of cases (66.1%), whereas lesions (benign, malignant) showed no predominant diffusion direction in the majority of cases (23.9%). ADC values showed highest differences between benign and malignant lesions (P<0.001) with resulting area under the curve (AUC) of 0.899. FA values were lower in benign (interquartile range, IR, 0.14-0.24) compared to malignant lesions (IR 0.21-0.35, P<0.002) with an AUC of 0.751-0.770. Following LRA, FA did not prove to have incremental value for differential diagnosis over ADC values. CONCLUSIONS Microanatomical differences between benign and malignant breast lesions as well as breast parenchyma can be visualized by using DTI.
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Affiliation(s)
- Pascal A T Baltzer
- Institute of Diagnostic and Interventional Radiology, Friedrich Schiller University Jena, Erlanger Allee 101, 07740, Jena, Germany.
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Dietzel M, Baltzer PAT, Vag T, Herzog A, Gajda M, Camara O, Kaiser WA. The adjacent vessel sign on breast MRI: new data and a subgroup analysis for 1,084 histologically verified cases. Korean J Radiol 2010; 11:178-86. [PMID: 20191065 PMCID: PMC2827781 DOI: 10.3348/kjr.2010.11.2.178] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2009] [Accepted: 11/02/2009] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE The adjacent vessel sign (AVS) is a descriptor for differentiating malignant from benign breast lesions on breast MRI (bMRI). This investigation was designed to verify the previous reports on the diagnostic accuracy of AVS and to assess correlation between AVS, histopathological diagnosis, lesion size and lesion grade. MATERIALS AND METHODS This study was approved by the local ethical committee. Experienced radiologists evaluated 1,084 lesions. The exclusion criteria were no histological verification after bMRI and breast interventions that were done up to one year before bMRI (surgery, core biopsy, chemo- or radiation therapy). The native and dynamic contrast-enhanced T1-weighted series were acquired using standardized protocols. The AVS was rated positive if a vessel leading to a lesion could be visualized. Prevalence of an AVS was correlated with the lesions' size, grade and histology using Chi-square-tests. RESULTS The AVS was significantly associated with malignancy (p < 0.001; sensitivity: 47%, specificity: 88%, positive-predictive-value [PPV]: 85%). Malignant lesions > 2 cm more often presented with an AVS than did those malignant lesions < 2 cm (p < 0.0001; sensitivity: 65%, PPV: 90%). There was no correlation of the AVS with the tumor grade. The prevalence of an AVS didn't significantly differ between invasive lobular carcinomas versus ductal carcinomas. In situ cancers were less frequently associated with an AVS (p < 0.001). CONCLUSION The adjacent vessel sign was significantly associated with malignancy. Thus, it can be used to accurately assess breast lesions on bMRI. In this study, the AVS was particularly associated with advanced and invasive carcinomas.
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Affiliation(s)
- Matthias Dietzel
- Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07740 Jena, Germany.
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Kolwijck E, Engelke UF, van der Graaf M, Heerschap A, Blom HJ, Hadfoune M, Buurman WA, Massuger LF, Wevers RA. N-acetyl resonances in in vivo and in vitro NMR spectroscopy of cystic ovarian tumors. NMR IN BIOMEDICINE 2009; 22:1093-9. [PMID: 19593761 DOI: 10.1002/nbm.1417] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
An unassigned and prominent resonance in the region from delta 2.0-2.1 ppm has frequently been found in the in vivo MR spectra of cancer patients. We demonstrated the presence of this resonance with in vivo MRS in the cyst fluid of a patient with an ovarian tumor. (1)H-NMRS on the aspirated cyst fluid of this patient confirmed the observation. A complex of resonances was observed between 2.0 and 2.1 ppm. It was also present in 11 additional ovarian cyst fluid samples randomly chosen from our biobank. The resonance complex was significantly more prominent in samples from mucinous tumors than in samples from other histological subtypes. A macromolecule (>10 kDa) was found responsible for this complex of resonances. A correlation spectroscopy (COSY) experiment revealed cross peaks of two different types of bound sialic acid suggesting that N-glycans from glycoproteins and/or glycolipids cause this resonance complex. In the literature, plasma alpha-1 acid glycoprotein (AGP), known for its high content of N-linked glycans, has been suggested to contribute to the delta 2.0-2.1 spectral region. The AGP cyst fluid concentration did not correlate significantly with the peak height of the delta 2.0-2.1 resonance complex in our study. AGP may be partly responsible for the resonance complex but other N-acetylated glycoproteins and/or glycolipids also contribute. After deproteinization of the cyst fluid, N-acetyl-L-aspartic acid (NAA) was found to contribute significantly to the signal in this spectral region in three of the 12 samples. GC-MS independently confirmed the presence of NAA in high concentration in the three samples, which all derived from benign serous tumors. We conclude that both NAA and N-acetyl groups from glycoproteins and/or glycolipids may contribute to the delta 2.0-2.1 ppm resonance complex in ovarian cyst fluid. This spectral region seems to contain resonances from biomarkers that provide relevant clinical information on the type of ovarian tumor.
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Affiliation(s)
- Eva Kolwijck
- Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
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