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Selby W, Garland P, Mastikhin I. Transient shear wave elastometry using a portable magnetic resonance sensor. Magn Reson Med 2025; 94:373-385. [PMID: 39869494 DOI: 10.1002/mrm.30444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 12/06/2024] [Accepted: 01/13/2025] [Indexed: 01/29/2025]
Abstract
PURPOSE Magnetic resonance elastography (MRE) provides detailed maps of tissue stiffness, helping to diagnose various health conditions, but requires the use of expensive clinical MRI scanners. Our approach utilizes compact, cost-effective portable MR sensors that offer bulk characterization of material properties in a region of interest close to the surface (within 1-2 cm). This accessible instrument could enable routine monitoring and prevention of diseases not readily evaluated with conventional tools. METHODS The method was tested on tissue-mimicking phantoms with varying stiffness. The gels were excited with acoustic pulses (one cycle of a sinusoidal waveform) at a fixed distance from the MR sensor. A series of delays between acoustic excitation and MR signal detection allowed time for the pulse to travel to the sensitive region. RESULTS The "arrival time" of the shear wave, determined by the time-dependent MR signal response, was used to calculate the shear wave speed. MR measurements of shear wave speed were compared with optical sensor measurements and manufacturer-tabulated values, aligning with expected relative differences between samples. CONCLUSION A portable MR-based transient elastometry technique for measuring tissue elasticity was developed and demonstrated on tissue-mimicking phantoms. Future improvements include using a new portable magnet to investigate depth-dependent changes in elasticity in stratified samples and integrating MR relaxation and diffusion measurements for comprehensive tissue analysis. This approach can complement conventional MRE in applications where a portable, affordable, and localized assessment of tissue stiffness is required.
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Affiliation(s)
- William Selby
- MRI Research Centre, Physics, University of New Brunswick, Fredericton, New Brunswick, Canada
| | - Phil Garland
- Mechanical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada
| | - Igor Mastikhin
- MRI Research Centre, Physics, University of New Brunswick, Fredericton, New Brunswick, Canada
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2
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Muslu Y, Tamada D, Roberts NT, Cashen TA, Mandava S, Kecskemeti SR, Hernando D, Reeder SB. Free-breathing, fat-corrected T 1 mapping of the liver with stack-of-stars MRI, and joint estimation of T 1, PDFF, R 2 * , and B 1 + . Magn Reson Med 2024; 92:1913-1932. [PMID: 38923009 DOI: 10.1002/mrm.30182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 05/03/2024] [Accepted: 05/16/2024] [Indexed: 06/28/2024]
Abstract
PURPOSE Quantitative T1 mapping has the potential to replace biopsy for noninvasive diagnosis and quantitative staging of chronic liver disease. Conventional T1 mapping methods are confounded by fat andB 1 + $$ {B}_1^{+} $$ inhomogeneities, resulting in unreliable T1 estimations. Furthermore, these methods trade off spatial resolution and volumetric coverage for shorter acquisitions with only a few images obtained within a breath-hold. This work proposes a novel, volumetric (3D), free-breathing T1 mapping method to account for multiple confounding factors in a single acquisition. THEORY AND METHODS Free-breathing, confounder-corrected T1 mapping was achieved through the combination of non-Cartesian imaging, magnetization preparation, chemical shift encoding, and a variable flip angle acquisition. A subspace-constrained, locally low-rank image reconstruction algorithm was employed for image reconstruction. The accuracy of the proposed method was evaluated through numerical simulations and phantom experiments with a T1/proton density fat fraction phantom at 3.0 T. Further, the feasibility of the proposed method was investigated through contrast-enhanced imaging in healthy volunteers, also at 3.0 T. RESULTS The method showed excellent agreement with reference measurements in phantoms across a wide range of T1 values (200 to 1000 ms, slope = 0.998 (95% confidence interval (CI) [0.963 to 1.035]), intercept = 27.1 ms (95% CI [0.4 54.6]), r2 = 0.996), and a high level of repeatability. In vivo imaging studies demonstrated moderate agreement (slope = 1.099 (95% CI [1.067 to 1.132]), intercept = -96.3 ms (95% CI [-82.1 to -110.5]), r2 = 0.981) compared to saturation recovery-based T1 maps. CONCLUSION The proposed method produces whole-liver, confounder-corrected T1 maps through simultaneous estimation of T1, proton density fat fraction, andB 1 + $$ {B}_1^{+} $$ in a single, free-breathing acquisition and has excellent agreement with reference measurements in phantoms.
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Affiliation(s)
- Yavuz Muslu
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Daiki Tamada
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | | | | | | | | | - Diego Hernando
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Electrical and Computer Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Scott B Reeder
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Department of Emergency Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
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3
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Tarchi SM, Salvatore M, Lichtenstein P, Sekar T, Capaccione K, Luk L, Shaish H, Makkar J, Desperito E, Leb J, Navot B, Goldstein J, Laifer S, Beylergil V, Ma H, Jambawalikar S, Aberle D, D'Souza B, Bentley-Hibbert S, Marin MP. Radiology of fibrosis part II: abdominal organs. J Transl Med 2024; 22:610. [PMID: 38956593 PMCID: PMC11218138 DOI: 10.1186/s12967-024-05346-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/25/2024] [Indexed: 07/04/2024] Open
Abstract
Fibrosis is the aberrant process of connective tissue deposition from abnormal tissue repair in response to sustained tissue injury caused by hypoxia, infection, or physical damage. It can affect almost all organs in the body causing dysfunction and ultimate organ failure. Tissue fibrosis also plays a vital role in carcinogenesis and cancer progression. The early and accurate diagnosis of organ fibrosis along with adequate surveillance are helpful to implement early disease-modifying interventions, important to reduce mortality and improve quality of life. While extensive research has already been carried out on the topic, a thorough understanding of how this relationship reveals itself using modern imaging techniques has yet to be established. This work outlines the ways in which fibrosis shows up in abdominal organs and has listed the most relevant imaging technologies employed for its detection. New imaging technologies and developments are discussed along with their promising applications in the early detection of organ fibrosis.
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Affiliation(s)
- Sofia Maria Tarchi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA.
| | - Mary Salvatore
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Philip Lichtenstein
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Thillai Sekar
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Kathleen Capaccione
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Lyndon Luk
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Hiram Shaish
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Jasnit Makkar
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Elise Desperito
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Jay Leb
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Benjamin Navot
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Jonathan Goldstein
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Sherelle Laifer
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Volkan Beylergil
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Hong Ma
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Sachin Jambawalikar
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Dwight Aberle
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Belinda D'Souza
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Monica Pernia Marin
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
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4
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Gu D, Lu Y, Xu B, Tang X. Sex-Specific Contribution of Cardiometabolic Index in Predicting Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from a General Population. Diabetes Metab Syndr Obes 2023; 16:3871-3883. [PMID: 38054037 PMCID: PMC10695138 DOI: 10.2147/dmso.s437413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 11/20/2023] [Indexed: 12/07/2023] Open
Abstract
Background and Objective Evidence suggests that cardiometabolic index (CMI) has been identified as a novel obesity-related index associated with diabetes, hypertension, and cardiovascular disease. Current evidence suggests that the differences in sex hormones and regional fat distribution in both sexes are directly correlated with metabolic dysfunction-associated fatty liver disease (MAFLD) risk. This study aimed to investigate the diagnostic value of CMI in MAFLD in both sexes. Methods This retrospective study included 6107 subjects who underwent annual health check-ups from March 2021 to January 2022. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariable logistic regression analysis and restricted cubic spline were used to investigate the association of CMI and MAFLD risk. Receiver operating characteristic curve analysis was conducted for the exploration of the diagnostic accuracies of obesity-related indicators. Areas under the curves (AUCs) with 95% CIs were calculated. Results Prevalence of MAFLD increased with elevated quartiles of CMI in both sexes. The median (IQR) age was 46.00 (18.00) years. Multivariate logistic regression analyses showed that higher CMI was independently associated with MAFLD, in which every additional standard deviation (SD) of CMI increased the risk of MAFLD (OR=2.72, 95% CI:2.35-3.15 for males; OR=3.26, 95% CI:2.36-4.51 for females). Subjects in the fourth quartile of CMI had the highest odds of MAFLD for males (OR=15.82, 95% CI:11.84-21.14) and females (OR=22.60, 95% CI:9.52-53.65)(all P for trend<0.001). Besides, CMI had a non-linearity association with MAFLD (all P for non-linearity<0.001). Furthermore, CMI exhibited the largest AUC compared to other obesity-related indexes in terms of discriminating MAFLD in males (AUC=0.796, 95% CI:0.782-0.810) and females (AUC=0.853, 95% CI:0.834-0.872). Conclusion CMI was a convenient indicator for the screening of MAFLD among Chinese adults. Females with high CMI had a better diagnostic value for MAFLD than males.
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Affiliation(s)
- Dongxing Gu
- Health Examination Center, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Yayun Lu
- Health Examination Center, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Baiqing Xu
- Health Examination Center, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Xuefeng Tang
- Department of Health Nursing, Huadong Sanatorium, Wuxi, People’s Republic of China
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5
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Ozturk A, Kumar V, Pierce TT, Li Q, Baikpour M, Rosado-Mendez I, Wang M, Guo P, Schoen S, Gu Y, Dayavansha S, Grajo JR, Samir AE. The Future Is Beyond Bright: The Evolving Role of Quantitative US for Fatty Liver Disease. Radiology 2023; 309:e223146. [PMID: 37934095 PMCID: PMC10695672 DOI: 10.1148/radiol.223146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 04/18/2023] [Accepted: 05/08/2023] [Indexed: 11/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common cause of morbidity and mortality. Nonfocal liver biopsy is the historical reference standard for evaluating NAFLD, but it is limited by invasiveness, high cost, and sampling error. Imaging methods are ideally situated to provide quantifiable results and rule out other anatomic diseases of the liver. MRI and US have shown great promise for the noninvasive evaluation of NAFLD. US is particularly well suited to address the population-level problem of NAFLD because it is lower-cost, more available, and more tolerable to a broader range of patients than MRI. Noninvasive US methods to evaluate liver fibrosis are widely available, and US-based tools to evaluate steatosis and inflammation are gaining traction. US techniques including shear-wave elastography, Doppler spectral imaging, attenuation coefficient, hepatorenal index, speed of sound, and backscatter-based estimation have regulatory clearance and are in clinical use. New methods based on channel and radiofrequency data analysis approaches have shown promise but are mostly experimental. This review discusses the advantages and limitations of clinically available and experimental approaches to sonographic liver tissue characterization for NAFLD diagnosis as well as future applications and strategies to overcome current limitations.
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Affiliation(s)
- Arinc Ozturk
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Viksit Kumar
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Theodore T. Pierce
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Qian Li
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Masoud Baikpour
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Ivan Rosado-Mendez
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Michael Wang
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Peng Guo
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Scott Schoen
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Yuyang Gu
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Sunethra Dayavansha
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Joseph R. Grajo
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
| | - Anthony E. Samir
- From the Center for Ultrasound Research & Translation,
Department of Radiology, Massachusetts General Hospital, 101 Merrimac St, 3rd
Floor, 323G, Boston, MA 02114 (A.O., V.K., T.T.P., Q.L., M.B., P.G., S.S., Y.G.,
S.D., A.E.S.); Harvard Medical School, Boston, Mass (A.O., V.K., T.T.P, Q.L.,
A.E.S.); Departments of Medical Physics and Radiology, University of Wisconsin,
Madison, Wis (I.R.M.); GE HealthCare, Milwaukee, Wis (M.W.); and Department of
Radiology, University of Florida, Gainesville, Fla (J.R.G.)
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6
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Yang Y, Jia X, Qu M, Yang X, Fang Y, Ying X, Zhang M, Wei J, Pan Y. Exploring the potential of treating chronic liver disease targeting the PI3K/Akt pathway and polarization mechanism of macrophages. Heliyon 2023; 9:e17116. [PMID: 37484431 PMCID: PMC10361319 DOI: 10.1016/j.heliyon.2023.e17116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/01/2023] [Accepted: 06/07/2023] [Indexed: 07/25/2023] Open
Abstract
Chronic liver disease is a significant public health issue that can lead to considerable morbidity and mortality, imposing an enormous burden on healthcare resources. Understanding the mechanisms underlying chronic liver disease pathogenesis and developing effective treatment strategies are urgently needed. In this regard, the activation of liver resident macrophages, namely Kupffer cells, plays a vital role in liver inflammation and fibrosis. Macrophages display remarkable plasticity and can polarize into different phenotypes according to diverse microenvironmental stimuli. The polarization of macrophages into M1 pro-inflammatory or M2 anti-inflammatory phenotypes is regulated by complex signaling pathways such as the PI3K/Akt pathway. This review focuses on investigating the potential of using plant chemicals targeting the PI3K/Akt pathway for treating chronic liver disease while elucidating the polarization mechanism of macrophages under different microenvironments. Studies have demonstrated that inhibiting M1-type macrophage polarization or promoting M2-type polarization can effectively combat chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, and liver fibrosis. The PI3K/Akt pathway acts as a pivotal modulator of macrophage survival, migration, proliferation, and their responses to metabolism and inflammatory signals. Activating the PI3K/Akt pathway induces anti-inflammatory cytokine expression, resulting in the promotion of M2-like phenotype to facilitate tissue repair and resolution of inflammation. Conversely, inhibiting PI3K/Akt signaling could enhance the M1-like phenotype, which exacerbates liver damage. Targeting the PI3K/Akt pathway has tremendous potential as a therapeutic strategy for regulating macrophage polarization and activity to treat chronic liver diseases with plant chemicals, providing new avenues for liver disease treatment.
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Affiliation(s)
- Yaqian Yang
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Xiaotao Jia
- Department of Neurology, The Affifiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710003, PR China
| | - Mengyang Qu
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Xinmao Yang
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Yan Fang
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Xiaoping Ying
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Meiqian Zhang
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Jing Wei
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Yanfang Pan
- Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
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7
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Low G, Ferguson C, Locas S, Tu W, Manolea F, Sam M, Wilson MP. Multiparametric MR assessment of liver fat, iron, and fibrosis: a concise overview of the liver "Triple Screen". Abdom Radiol (NY) 2023; 48:2060-2073. [PMID: 37041393 DOI: 10.1007/s00261-023-03887-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/12/2023] [Accepted: 03/13/2023] [Indexed: 04/13/2023]
Abstract
Chronic liver disease (CLD) is a common source of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) serves as a major cause of CLD with a rising annual prevalence. Additionally, iron overload can be both a cause and effect of CLD with a negative synergistic effect when combined with NAFLD. The development of state-of-the-art multiparametric MR solutions has led to a change in the diagnostic paradigm in CLD, shifting from traditional liver biopsy to innovative non-invasive methods for providing accurate and reliable detection and quantification of the disease burden. Novel imaging biomarkers such as MRI-PDFF for fat, R2 and R2* for iron, and liver stiffness for fibrosis provide important information for diagnosis, surveillance, risk stratification, and treatment. In this article, we provide a concise overview of the MR concepts and techniques involved in the detection and quantification of liver fat, iron, and fibrosis including their relative strengths and limitations and discuss a practical abbreviated MR protocol for clinical use that integrates these three MR biomarkers into a single simplified MR assessment. Multiparametric MR techniques provide accurate and reliable non-invasive detection and quantification of liver fat, iron, and fibrosis. These techniques can be combined in a single abbreviated MR "Triple Screen" assessment to offer a more complete metabolic imaging profile of CLD.
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Affiliation(s)
- Gavin Low
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada
| | - Craig Ferguson
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada
| | - Stephanie Locas
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada
| | - Wendy Tu
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada
| | - Florin Manolea
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada
| | - Medica Sam
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada
| | - Mitchell P Wilson
- Department of Radiology and Diagnostic Imaging, University of Alberta Hospital, WMC 2B2.41 8440-112 ST, Edmonton, AB, T6G2B7, Canada.
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Lavin B, Eykyn TR, Phinikaridou A, Xavier A, Kumar S, Buqué X, Aspichueta P, Sing-Long C, Arrese M, Botnar RM, Andia ME. Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS -/- mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. NMR IN BIOMEDICINE 2023:e4932. [PMID: 36940044 DOI: 10.1002/nbm.4932] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 03/08/2023] [Accepted: 03/09/2023] [Indexed: 06/18/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS-/- mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3 T. After 8 weeks of diet intervention, eNOS-/- mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by 1 H-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3-/- mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and 1 H-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS-/- murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.
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Affiliation(s)
- Begoña Lavin
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK
- BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK
- Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain
| | - Thomas R Eykyn
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK
- BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK
| | - Alkystis Phinikaridou
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK
- BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK
| | - Aline Xavier
- Biomedical Engineering, Faculty of Engineering, Universidad de Santiago de Chile, Santiago, Chile
- ANID - Millennium Science Initiative Program - Millennium Institute Intelligent Healthcare Engineering, Santiago, Chile
| | - Shravan Kumar
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK
| | - Xabier Buqué
- Physiology Department, School of Medicine and Nursing, Universidad del País Vasco UPV/EHU, Vizcaya, Spain
- Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
| | - Patricia Aspichueta
- Physiology Department, School of Medicine and Nursing, Universidad del País Vasco UPV/EHU, Vizcaya, Spain
- Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
- CIBER de enfermedades hepáticas y digestivas (CIBERehd), Spain
| | - Carlos Sing-Long
- ANID - Millennium Science Initiative Program - Millennium Institute Intelligent Healthcare Engineering, Santiago, Chile
- School of Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- ANID - Millennium Science Initiative Program - Millennium Institute Intelligent Healthcare Engineering, Santiago, Chile
- Gastroenterology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - René M Botnar
- School of Biomedical Engineering Imaging Sciences, King's College London, London, UK
- BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London, UK
- ANID - Millennium Science Initiative Program - Millennium Institute Intelligent Healthcare Engineering, Santiago, Chile
- School of Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marcelo E Andia
- ANID - Millennium Science Initiative Program - Millennium Institute Intelligent Healthcare Engineering, Santiago, Chile
- School of Medicine and Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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Duan S, Yang D, Xia H, Ren Z, Chen J, Yao S. Cardiometabolic index: A new predictor for metabolic associated fatty liver disease in Chinese adults. Front Endocrinol (Lausanne) 2022; 13:1004855. [PMID: 36187093 PMCID: PMC9523727 DOI: 10.3389/fendo.2022.1004855] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 08/29/2022] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE Cardiometabolic index (CMI) is a well promising indicator for predicting obesity-related diseases, but its predictive value for metabolic associated fatty liver disease (MAFLD) is unclear. This study aimed to investigate the relationship between CMI and MAFLD and to evaluate the predictive value of CMI for MAFLD. METHODS A total of 943 subjects were enrolled in this cross-sectional study. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariate logistic regression analysis was used to systematically evaluate the relationship between CMI and MAFLD. Receiver operating characteristic (ROC) curves were used to assess the predictive power of CMI for MAFLD and to determine the optimal cutoff value. The diagnostic performance of high CMI for MAFLD was validated in 131 subjects with magnetic resonance imaging diagnosis. RESULTS Subjects with higher CMI exhibited a significantly increased risk of MAFLD. The odds ratio for a 1-standard-deviation increase in CMI was 3.180 (2.102-4.809) after adjusting for various confounding factors. Further subgroup analysis showed that there were significant additive interactions between CMI and MAFLD risk in gender, age, and BMI (P for interaction < 0.05), and the area under the ROC curve(AUC) of CMI for predicting MAFLD were significantly higher in female, young, and nonobese subgroups than that in male, middle-aged and elderly, and obese subgroups (all P < 0.05). Moreover, among nonobese subjects, the AUC of CMI was significantly higher than that of waist circumference, BMI, TG/HDL-C, and TG (all P < 0.05). The best cutoff values of CMI to diagnose MAFLD in males and females were 0.6085 and 0.4319, respectively, and the accuracy, sensitivity, and specificity of high CMI for diagnosing MAFLD in the validation set were 85.5%, 87.5%, and 80%, respectively. CONCLUSIONS CMI was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD. High CMI had excellent diagnostic performance for MALFD, which can enable important clinical value for early identification and screening of MAFLD.
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Affiliation(s)
- Shaojie Duan
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Deshuang Yang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Integrative Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Hui Xia
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Zhiying Ren
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Jialiang Chen
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shukun Yao
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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Intra-patient comparison of 3D and 2D magnetic resonance elastography techniques for assessment of liver stiffness. Abdom Radiol (NY) 2022; 47:998-1008. [PMID: 34982182 DOI: 10.1007/s00261-021-03355-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE To evaluate performance of 3D magnetic resonance elastography (MRE) using spin-echo echo-planar imaging (seEPI) for assessment of hepatic stiffness compared with 2D gradient-recalled echo (GRE) and 2D seEPI sequences. METHODS Fifty-seven liver MRE examinations including 2D GRE, 2D seEPI, and 3D seEPI sequences were retrospectively evaluated. Elastograms were analyzed by 2 radiologists and polygonal regions of interests (ROIs) were drawn in 2 different fashions: "curated" ROI (avoiding liver edge, major vessels, and areas of wave interferences) and "non-curated" ROI (including largest cross section of liver, to assess the contribution of artifacts). Liver stiffness measurement (LSM) was calculated as the arithmetic mean of individual stiffness values for each technique. For 3D MRE, LSMs were also calculated based on 4 slices ("abbreviated LSM"). Intra-patient variations in LSMs and different methods of ROI placement were assessed by univariate tests. A p-value of < 0.05 was set as a statistically significant difference. RESULTS Mean surface areas of the ROIs were 50,723 mm2, 12,669 mm2, 5814 mm2, and 10,642 mm2 for 3D MRE, abbreviated 3D MRE, 2D GRE, and 2D seEPI, respectively. 3D LSMs based on curated and non-curated ROIs showed no clinically significant difference, with a mean difference less than 0.1 kPa. Abbreviated 3D LSMs had excellent correlation with 3D LSMs based on all slices (r = 0.9; p < 0.001) and were not significantly different (p = 0.927). CONCLUSION 3D MRE allows more reproducible measurements due to its lower susceptibility to artifacts and provides larger areas of parenchyma, enabling a more comprehensive evaluation of the liver.
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Automated CNN-Based Analysis Versus Manual Analysis for MR Elastography in Nonalcoholic Fatty Liver Disease: Inter-method Agreement and Fibrosis Stage Discriminative Performance. AJR Am J Roentgenol 2022; 219:224-232. [PMID: 35107306 DOI: 10.2214/ajr.21.27135] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background: Histological fibrosis stage is the most important prognostic factor in chronic liver disease. MR elastography (MRE) is the most accurate noninvasive method for detecting and staging liver fibrosis. Although accurate, manual ROI-based MRE analysis is complex, time consuming, requires specialized readers, and prone to methodologic variability and suboptimal inter-reader agreement. Objectives: To develop an automated convolutional neural network (CNN)-based method for liver MRE analysis, evaluate its agreement with manual ROI-based analysis, and assess its discriminative performance for dichotomized fibrosis stages using histology as reference standard. Methods: In this retrospective cross-sectional study, 675 participants who underwent MRE using different MRI systems and field strengths at 28 imaging sites from five multicenter international clinical trials of nonalcoholic steatohepatitis were included for algorithm development and internal testing of agreement between automated CNN- and manual ROI-based analyses. Eighty-one patients (52 women, 29 men; mean age, 54 years) who underwent MRE using a single 3-Tesla system and liver biopsy for clinical purposes at a single institution were included for external testing of agreement and assessment of fibrosis stage discriminative performance. Agreement was evaluated using intra-class correlation coefficients (ICC). 95% CIs were computed using bootstrapping. Discriminative performance of each method for dichotomized histologic fibrosis stage was evaluated by AUC and compared using bootstrapping. Results: Mean CNN- and manual ROI-based stiffness measurements ranged from 3.21 to 3.34 kPa in trial participants and from 3.30 to 3.45 kPa in clinical patients. ICC for CNN- and manual ROI-based measurements was 0.98 (95% CI, 0.978-0.98) in trial participants and 0.99 (95% CI: 0.98-0.99) in clinical patients. AUC for classification of dichotomized fibrosis stage ranged from 0.89-0.93 for CNN- and 0.87-0.93 for manual ROI-based analyses (p=.23-.75). Conclusion: Stiffness measurements using the automated CNN-based method agreed strongly with manual ROIbased analysis across MRI systems and field strengths, with excellent discriminative performance for histology-determined dichotomized fibrosis stages in external testing. Clinical Impact: Given the high incidence of chronic liver disease worldwide, it is important that noninvasive tools to assess fibrosis are applied reliably across different settings. CNN-based analysis is feasible and may reduce reliance on expert image analysts.
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Chang SD, Cunha GM, Chernyak V. MR Imaging Contrast Agents: Role in Imaging of Chronic Liver Diseases. Magn Reson Imaging Clin N Am 2021; 29:329-345. [PMID: 34243921 DOI: 10.1016/j.mric.2021.05.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Contrast-enhanced MR imaging plays an important role in the evaluation of patients with chronic liver disease, particularly for detection and characterization of liver lesions. The two most commonly used contrast agents for liver MR imaging are extracellular agents (ECAs) and hepatobiliary agents (HBAs). In patients with liver disease, the main advantage of ECA-enhanced MR imaging is its high specificity for the diagnosis of progressed HCCs. Conversely, HBAs have an additional contrast mechanism, which results in high liver-to-lesion contrast and highest sensitivity for lesion detection in the hepatobiliary phase. Emerging data suggest that features depicted on contrast-enhanced MR imaging scans are related to tumor biology and are predictive of patients' prognosis, likely to further expand the role of contrast-enhanced MR imaging in the clinical care of patients with chronic liver disease.
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Affiliation(s)
- Silvia D Chang
- Department of Radiology, University of British Columbia, Vancouver General Hospital, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9, Canada. https://twitter.com/SilviaChangMD
| | - Guilherme Moura Cunha
- Department of Radiology, University of Washington, 1959 NE Pacific Street 2nd Floor, Seattle, WA 98195, USA
| | - Victoria Chernyak
- Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
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