Stefan Ruschke1, Amber Pokorney2, Holger Eggers3, Jan S. Kirschke4, Thomas Baum5, Dimitrios C. Karampinos1, and Houchun Harry Hu2
1Diagnostic and Interventional Radiology, Technische Universität München, Munich, Germany, 2Radiology, Phoenix Children's Hospital, Phoenix, AZ, United States, 3Philips Research, Hamburg, Germany, 4Section of Diagnostic and Interventional Neuroradiology, Technische Universität München, Munich, Germany, 5Department of Diagnostic and Interventional Radiology, Technische Universität München, Munich, Germany
Synopsis
In this work, we describe our
preliminary clinical experience using a previously reported time-interleaved
six-echo gradient-echo (TIMGRE) acquisition for water-fat chemical-shift
encoded MRI. The acquisition scheme involved two interleaves that
acquired three echoes each with fly-back gradients. The pulse sequence
was used to quantify vertebral bone marrow fat fraction in a pilot cohort of 12
pediatric patients (age range: 1-13 years) at 3T with 1.2-1.6 mm in-plane
resolution and 1.2-3 mm slices. The knowledge on bone marrow fat fraction may provide insight into adverse effects on bone health later
in life, given that there is clinical relevance of vertebral
osteoporotic fractures in adults. Introduction
In recent years, there has been a
significant increase in the utilization of MR imaging and spectroscopy to
quantify vertebral bone marrow fat content [1-4]. Multiple independent
groups have demonstrated that vertebral bone marrow fat content is a useful
imaging biomarker in the characterization of bone health [5-6], metabolic
disorders [7], and cancer [8-9]. While a majority of the works thus far
has been focused in adults and older aging populations, similar vertebral bone
marrow fat content data in children remain limited. The capability to
robustly and accurately quantify vertebral bone marrow fat content in children
may help better understanding the bone development process at an early age [10]
and provide insight into potential effects on adverse bone health later in
life. However, pediatric imaging usually requires smaller voxel sizes than
adult imaging, leading to increased echo time steps in water-fat imaging. The
objective of this work was to demonstrate the feasibility of a previously reported
time-interleaved multi-echo gradient-echo (TIMGRE) water-fat “Dixon” pulse
sequence [11], allowing the flexible selection of echo times independently of
voxel size for robust water-fat decomposition in pediatric imaging. Furthermore,
a complex-based multi-peak water-fat model with single T2* estimation in TIMGRE
ensures robust proton-density fat fraction determination.
Materials and Methods
Figure 1 depicts the TIMGRE sequence.
The 3D acquisition scheme acquires six echoes using fly-back gradients in two
interleaves with three echoes each. The interleaf offset time was chosen to achieve
a constant echo spacing between consecutive echoes. A previously described phase correction procedure [11] was used. It corrects phase inconsistencies from concomitant
fields between the two interleaves and linear phase variations along the readout
direction.
All studies were performed on two
3T Ingenia MR whole-body systems (Philips Healthcare). The built-in posterior coil array in the
scanner table was used for signal reception. The addition of the TIMGRE
water-fat pulse sequence was approved by the institutional review board. The cohort of pediatric patients studied thus
far (4M, 8F, age range: 1-13 years, 5.1+/-3.2 years) were receiving routine spine MRI examinations
for clinically indicated reasons and general anesthesia was used in all cases in accordance with institutional protocol. Typical TIMGRE imaging parameters used in this study
were: 16-26 sagittal slices, slice thickness: 1.2 to 3 mm, S/I and A/P FOV: 360
to 500 mm and 140 to 240 mm, in-plane voxel resolution: 1.2-1.6 mm, no SENSE
acceleration and no partial Fourier sampling, flip angle: 3 degrees, TR: 8.8-12.9
ms, effective TE spacing 1.2-1.3 ms, first TE: 1.5-1.7 ms, total scan time: 2-3
min.
Results
Figure 2 illustrates
representative whole-spine examples from five of the 12 patients, using a color
scale from 0-100% for the proton-density fat fraction. Figure 3 plots representative average fat
fraction values measured from regions-of-interests drawn along the five lumbar
vertebra sections in the 12 patients.
The data is further split into two groups, one with patients (n=9) that
showed no spinal abnormalities on their exam (black symbols), and one with
patients (n=3) that exhibited clinically relevant pathology (red symbols). Particularly in the former group, the data
suggests an age dependence in the vertebral bone marrow fat fraction (r2 = 0.58 linear fit, r2 = 0.68 exponential fit) that is
visible by MR imaging and manifests early in childhood development.
Discussion and Conclusion
In this pilot work, we have
demonstrated preliminary feasibility of a high spatial resolution TIMGRE
water-fat pulse sequence for vertebral bone marrow fat quantification in a
small cohort of pediatric patients. Our study is ongoing as we continue to
accumulate more pediatric data to assess age- and gender- dependence on
vertebral bone marrow fat content [2]. The age dependence of the bone marrow
fat fraction has been previously studied extensively in adults [2, 12], but not
in children. In adults, it is known that age-related increase in vertebral
marrow adiposity is associated with bone loss and reduction in bone mineral
density [5]. In children, there is limited literature on the red to yellow
marrow conversion in long bones [13], but the association between bone formation
and marrow conversion in the spine remains largely unknown. A
non-invasive method to monitor age-related changes in vertebral bone marrow fat
fraction in children will help in understanding the relationship between
vertebral bone acquisition and marrow adipogenesis. The knowledge gained
in children will provide insight into potential adverse effects on bone health
later in life, given that there is a strong clinical relevance of vertebral
osteoporotic fractures in adults.
Acknowledgements
The
authors acknowledge Philips Healthcare for research support and the German
Academic Exchange Service (DAAD) for support through the
“Doktorandenstipendium”.References
[1] Bredella MA, et al., 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;
227(1):230-235.
[2] Baum T, et al., Assessment of whole spine
vertebral bone marrow fat using chemical shift-encoding based water-fat MRI. J Magn Reson Imaging 2015; 42(4):1018-1023.
[3] Martin J, et al., Rapid determination of vertebral
fat fraction over a large range of vertebral bodies. J Med
Imaging Radiat Oncol 2014; 58(2):155-163.
[4] Roldan-Valadez E, et al., Gender and age groups
interactions in the quantification of bone marrow fat content in lumbar spine
using 3T MR spectroscopy: a multivariate analysis of covariance (Mancova). Eur J Radiol 2013; 82(11):e697-702.
[5] Griffith JF, et al., Vertebral marrow fat content and
diffusion and perfusion indexes in women with varying bone density: MR
evaluation. Radiology 2006; 241(3):831-838.
[6] Karampinos D, et al., Association of MRS-based vertebral bone marrow fat fraction with bone strength in a human in vitro model. J Osteoporos 2015; 2015:152349. PMID: 25969766
[7] Mostoufi-Moab S, et al., Adverse fat depots and marrow adiposity are associated with skeletal deficits and insulin resistance in long-term survivors of pediatric hematopoietic stem cell transplantation. J Bone Miner Res 2015; 30(9):1657-1666.
[8] Schraml C, 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(4):1048-1056.
[9] Kim YP, et al., Differentiation between focal
malignant marrow-replacing lesions and benign red marrow deposition of the
spine with T2*-corrected fat-signal fraction map using a three-echo volume
interpolated breath-hold gradient echo Dixon sequence. Korean J
Radiol 2014; 15(6):781-791.
[10] Rosen CJ, et al., Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. Crit Rev Eukaryot Gene Expr 2009; 19(2):109-124.
[11] Ruschke S, et al., Addressing phase errors in quantitative water-fat imaging at 3T using a time-interleaved multi-echo gradient-echo acquisition. ISMRM 2015, abstract #3657.
[12] Griffith J, et al., Bone marrow fat content in the
elderly: a reversal of sex difference seen in younger subjects. J Magn Reson Imaging 2012; 36(1):225-230.
[13] Waitches G, et al., Sequence and rate of bone
marrow conversion in the femora of children as seen on MR imaging: are accepted
standards accurate? AJR Am
J Roentgenol 1994; 162(6):1399-1406.