Molecular In Vivo Imaging of Bone Marrow Adipose Tissue
Purpose of Review
The in vivo study of molecular processes in human bone marrow is important for both diagnostics and understanding of disease pathophysiology. Traditionally, the hematopoietic component of the bone marrow has been a research focus, but recently, the role of bone marrow adipose tissue has been gaining interest in many applications. The purpose of the present review is to give an overview of existing imaging modalities allowing in vivo molecular imaging of bone marrow adipose tissue in humans with an emphasis on technical aspects: the characteristics of the extracted parameters and their application in bone marrow adipose tissue.
Magnetic resonance (MR) imaging (MRI) and spectroscopy (MRS) are the most frequently used imaging methods for the examination of bone marrow adipose tissue as they provide rich soft tissue contrast and come without ionizing radiation. Existing MR methods allow the extraction of many different measures including proton density fat fraction, fatty acid characteristics, and diffusion and perfusion properties. However, many available techniques have to be carefully adjusted to be used in the investigation of the fat signal component, especially in the presence of trabecular bone. Dual-energy computed tomography (DECT) is an emerging technique—not yet widely available—which appears to be a promising alternative to MR for rapid fat fraction assessment. Positron emission tomography (PET) allows additional functional metabolic imaging and therefore provides valuable additional information (e.g., glucose uptake) to MR-based parameters at the cost of ionizing radiation.
Bone marrow imaging still appears to be a niche with remaining technical challenges using existing imaging modalities. A good working knowledge of the underlying physical and technical principles is required as most techniques are yet not available out of the box and may need to be adjusted to fit the requirements for bone marrow adipose tissue imaging. In summary, MR, DECT, and PET enable the measurement of several inherently different parameters in in vivo molecular imaging of bone marrow adipose tissue. The growing interest for molecular imaging markers of bone marrow, thanks to its high metabolic and clinical significance, may eventually lead to new developments, as well as improvements of emerging techniques as soon as they become more broadly available.
KeywordsMolecular imaging Bone marrow adipose tissue Bone marrow fat Bone marrow adipocytes Magnetic resonance imaging Magnetic resonance spectroscopy
Thomas Baum received grant support from the Technical University of Munich, Faculty of Medicine (KKF H01). Dimitrios C. Karampinos received grant support from Philips Healthcare.
Compliance with Ethical Standards
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Conflict of Interest
Stefan Ruschke, Maximilian N. Diefenbach, Daniela Franz, and Thomas Braum declare no conflicts of interest. Dimitrios C. Karampinos reports grants from Philips Healthcare, during the conduct of study and outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 11.Moulopoulos LA, Koutoulidis V. Bone marrow MRI: a pattern-based approach; 2015. p. 1–172.Google Scholar
- 16.Karampinos DC, Ruschke S, Dieckmeyer M, Diefenbach M, Franz D, Gersing AS, et al. Quantitative MRI and spectroscopy of bone marrow. J Magn Reson Imaging. 2017;7:448.Google Scholar
- 21.• Dieckmeyer M, Ruschke S, Cordes C, Yap SP, Kooijman H, Hauner H, et al. The need for T2 correction on MRS-based vertebral bone marrow fat quantification: implications for bone marrow fat fraction age dependence. NMR Biomed. 2015;28:432–9. This study shows the confounding effect of T2 weighting on MRS measurements in vertebral bone marrow and why PDFF should be measured instead of sFF. CrossRefPubMedGoogle Scholar
- 23.Hernando D, Sharma SD, Aliyari Ghasabeh M, et al. Multisite, multivendor validation of the accuracy and reproducibility of proton-density fat-fraction quantification at 1.5T and 3T using a fat-water phantom. Magn Reson Med. 2016; https://doi.org/10.1002/mrm.26228.
- 25.• Baum T, Yap SP, Dieckmeyer M, Ruschke S, Eggers H, Kooijman H, et al. Assessment of whole spine vertebral bone marrow fat using chemical shift-encoding based water-fat MRI. J Magn Reson Imaging. 2015;42:1018–23. Study on whole spine quantitative PDFF mapping achieving an absolute precision error of 1.7%. CrossRefPubMedGoogle Scholar
- 35.Fallone CJ, McKay RT, Yahya A. Long TE STEAM and PRESS for estimating fat olefinic/methyl ratios and relative ω-3 fat content at 3T. J Magn Reson Imaging. 2017;24:238.Google Scholar
- 36.Xu K, Sigurdsson S, Gudnason V, Hue T, Schwartz A, Li X. Reliable quantification of marrow fat content and unsaturation level using in vivo MR spectroscopy. Magn Reson Med. 2017;19:109.Google Scholar
- 38.• Dieckmeyer M, Ruschke S, Eggers H, Kooijman H, Rummeny EJ, Kirschke JS, et al. ADC quantification of the vertebral bone marrow water component: removing the confounding effect of residual fat. Magn Reson Med. 2016;46:601. Study showing the confounding effect of the lipid signal in quantitative diffusion-weighted MRI. Google Scholar
- 40.Dietrich O, Geith T, Reiser MF, Baur Melnyk A (2015) Diffusion imaging of the vertebral bone marrow. NMR Biomed n/a–n/a.Google Scholar
- 42.Biffar A, Schmidt GP, Sourbron S, D'Anastasi M, Dietrich O, Notohamiprodjo M, et al. Quantitative analysis of vertebral bone marrow perfusion using dynamic contrast-enhanced MRI: initial results in osteoporotic patients with acute vertebral fracture. J Magn Reson Imaging. 2011;33:676–83.CrossRefPubMedGoogle Scholar
- 53.• Bredella MA, Daley SM, Kalra MK, Brown JK, Miller KK, Torriani M. Marrow adipose tissue quantification of the lumbar spine by using dual-energy CT and single-voxel (1)H MR spectroscopy: a feasibility study. Radiology. 2015;277:230–5. In this study, Bredella et al. validate DECT for rapid bone marrow fat fraction quantification against MRS. CrossRefPubMedPubMedCentralGoogle Scholar
- 59.Deloar HM, Fujiwara T, Nakamura T, Itoh M, Imai D, Miyake M, et al. Estimation of internal absorbed dose of <emphasis type=“SmallCaps”>l</emphasis>−[methyl-<superscript>11</superscript>C]methionine using whole-body positron emission tomography. Eur J Nucl Med. 1998;25:629–33.CrossRefPubMedGoogle Scholar
- 66.Maciel JG, de Araújo IM, Carvalho AL, Simão MN, Bastos CM, Troncon LEA, et al. Marrow fat quality differences by sex in healthy adults. 2016; https://doi.org/10.1016/j.jocd.2016.08.002.
- 69.Cohen A, Shen W, Dempster DW, Zhou H, Recker RR, Lappe JM, et al. Marrow adiposity assessed on transiliac crest biopsy samples correlates with noninvasive measurement of marrow adiposity by proton magnetic resonance spectroscopy ((1)H-MRS) at the spine but not the femur. Osteoporos Int. 2015;26:2471–8.CrossRefPubMedPubMedCentralGoogle Scholar
- 71.Salas-Ramirez M, Tran-Gia J, Kesenheimer C, Weng AM, Kosmala A, Heidemeier A, et al. Quantification of fat fraction in lumbar vertebrae: correlation with age and implications for bone marrow dosimetry in molecular radiotherapy. Phys Med Biol. 2017;63:025029. https://doi.org/10.1088/1361-6560/aa9a28.CrossRefGoogle Scholar
- 72.Aoki T, Yamaguchi S, Kinoshita S, Hayashida Y, Korogi Y. Quantification of bone marrow fat content using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): reproducibility, site variation and correlation with age and menopause. Br J Radiol. 2016;89:20150538.CrossRefPubMedPubMedCentralGoogle Scholar
- 74.•• Schraml C, Schmid M, Gatidis S, Schmidt H, la Fougère C, Nikolaou K, et al. Multiparametric analysis of bone marrow in cancer patients using simultaneous PET/MR imaging: correlation of fat fraction, diffusivity, metabolic activity, and anthropometric data. J Magn Reson Imaging. 2015;42:1048–56. Schraml et al. instigate for the first time connections between bone marrow metabolic function using PET and MR imaging parameters. CrossRefPubMedGoogle Scholar