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Phantom for assessment of fat suppression in large field-of-view diffusion-weighted magnetic resonance imaging
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Institute of Physics and Engineering in Medicine Phys. Med. Biol. 59 (2014) 2235–2248
Physics in Medicine and Biology
doi:10.1088/0031-9155/59/9/2235
Phantom for assessment of fat suppression in large field-of-view diffusion-weighted magnetic resonance imaging J M Winfield 1 , N H M Douglas 1 , N M deSouza 1,2 and D J Collins 1,2 1 CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK 2 Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK
E-mail: [email protected] Received 5 September 2013, revised 6 March 2014 Accepted for publication 21 March 2014 Published 8 April 2014 Abstract
We present the development and application of a phantom for assessment and optimization of fat suppression over a large field-of-view in diffusion-weighted magnetic resonance imaging at 1.5 T and 3 T. A Perspex cylinder (inner diameter 185 mm, height 300 mm) which contains a second cylinder (inner diameter 140 mm) was constructed. The inner cylinder was filled with water doped with copper sulphate and sodium chloride and the annulus was filled with corn oil, which closely matches the spectrum and longitudinal relaxation times of subcutaneous abdominal fat. Placement of the phantom on the couch at 45◦ to the z-axis presented an elliptical cross-section, which was of a similar size and shape to axial abdominal images. The use of a phantom for optimization of fat suppression allowed quantitative comparison between studies without the differences introduced by variability between human subjects. We have demonstrated that the phantom is suitable for selection of inversion delay times, spectral adiabatic inversion recovery delays and assessment of combinatorial methods of fat suppression. The phantom is valuable in protocol development and the assessment of new techniques, particularly in multi-centre trials. Keywords: test object, diffusion-weighted MRI, fat suppression (Some figures may appear in colour only in the online journal)
0031-9155/14/092235+14$33.00
© 2014 Institute of Physics and Engineering in Medicine Printed in the UK & the USA 2235
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1. Introduction Suppression of the signal from fat is essential in diffusion-weighted magnetic resonance imaging (DW-MRI) because qualitative interpretation requires that the overlying signal from unsuppressed chemical-shifted fat does not obscure features of interest in the image and quantitative analysis demands that the superposition of the fat signal on a region of interest does not affect estimation of the apparent diffusion coefficient (ADC). It is also helpful to eliminate fat from the ADC quantification in tissues such as bone marrow, omentum and steatotic liver when assessing malignant infiltration. Fat suppression techniques make use of the differences in the 1H MR spectra of water and fat or their differences in T1 relaxation times, or a combination of the two. The largest peak in the 1H MR spectrum of human fat occurs at 1.30 ppm (referred to here as the aliphatic fat signal since the resonances lie in the aliphatic region of the 1H MR spectrum) and is attributed to protons attached to saturated carbon atoms in CH2 groups together with multiple smaller adjacent peaks (0.90 ppm and 1.59 to 2.77 ppm) (Ren et al 2008). The signal from protons attached to water molecules occurs at 4.7 ppm. Unsuppressed signal from aliphatic fat is shifted relative to the water signal by several pixels in the phase-encode (PE) direction in echo-planar imaging (EPI) at 1.5 T and 3 T. Selective suppression of the aliphatic fat signal by saturation or inversion pulses used in frequency-selective fat suppression techniques, for example fat saturation (Fat Sat), spectral inversion recovery (SPIR) and spectral adiabatic inversion recovery (SPAIR), is therefore possible. Conversely, protons attached to unsaturated carbon atoms have a higher chemical shift than the water protons (5.31 ppm) (Ren et al 2008) and lie outside the narrow-bandwidth radiofrequency (RF) pulses used in spectrally-selective fat suppression techniques. The fat signal at 5.31 ppm will be referred to here as the olefinic fat signal since the resonances lie in the olefinic region of the 1H MR spectrum. The shift of the olefinic fat signal in an image, relative to the water signal, is smaller than the shift of the aliphatic fat signal and occurs in the opposite direction. SPAIR and SPIR use narrow-bandwidth RF pulses to selectively invert the aliphatic fat protons. These techniques use T1 properties in addition to spectral properties to suppress the fat signal making the T1 of the aliphatic fat resonances relevant in optimizing the sequences. Fat Sat uses a non-inverting narrow-bandwidth RF pulse to selectively saturate the aliphatic fat protons. Inhomogeneities in the B0 field that shift some of the aliphatic protons outside the frequency range of selective RF pulses result in imperfect fat suppression in SPAIR, SPIR and Fat Sat. Aliphatic fat resonances may also be suppressed by water-selective excitation (Water Ex) which uses narrow-bandwidth RF pulses to selectively excite the water protons (and also excites the adjacent olefinic fat protons) whilst leaving the aliphatic fat protons unexcited. Slice- selective gradient reversal (SSGR), which exploits the difference in resonant frequencies between on-resonance water protons and other off-resonance species (Park et al 1987, Gomori et al 1988, Nagy and Weiskopf 2008), suppresses aliphatic fat more than olefinic fat due to the larger frequency difference between aliphatic fat and water than between olefinic fat and water. SSGR also attenuates the signal from water protons which have been shifted to frequencies away from the main water resonance due to B0 inhomogeneities. There are therefore several challenges in achieving sequences with optimal suppression of the aliphatic and olefinic fat signals. Ethical considerations and volunteer time limit fat suppression sequence optimization in normal volunteers, which are additionally confounded by the natural variation in body habitus within and between subjects. A phantom provides stability, repeatability and measurement data for qualitative and quantitative comparisons between different fat suppression techniques and scanners. However, inappropriate phantoms may fail to reveal salient features in the 2236
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images, for example small phantoms may not reveal failures in fat suppression arising from inhomogeneities in the B0 field at the edges of a large field-of-view (FOV). Inappropriate choice of material for the fat may also produce poorer or better fat suppression than would be found in vivo due to mismatches between the spectra or T1 relaxation times of the material and human fat. Previous studies have reported results from small fat phantoms developed for protocol development in areas such as breast (Freed et al 2011), salivary glands (Juan et al 2009) and brain (Rice et al 1998). Phantoms have also been used to demonstrate new fat suppression techniques (Flask et al 2003, Hernando et al 2011, Kaldoudi et al 1993, Kuroda et al 1998, Ma et al 2002, 2005, Ma 2008, Nagy and Weiskopf 2008, Sarlls et al 2011, Wilm et al 2007). The purpose of this study therefore was to develop and evaluate a phantom for assessment of fat suppression for body DW-MRI that: (1) occupies a large FOV; (2) has a fat spectrum that matches the positions and relative intensities of the main fat resonances observed in vivo; (3) has longitudinal relaxation times that are closely matched to human fat at 1.5 T and 3 T; (4) is composed of stable, inexpensive and widely available materials; (5) has constituents that provide reasonable coil loading and avoid significant B1 inhomogeneities in order to determine optimal fat suppression protocols at 1.5 T and 3 T. In this study we will use the term ‘suppression’ to refer to the intended (desirable) removal of the fat signal from the images. We will use the term ‘attenuation’ to refer to the unintended or undesirable loss of water signal from the images, for example attenuation of water signal by inversion recovery (IR) or attenuation of off-resonant water by SSGR. 2. Materials and methods 2.1. Phantom construction
We constructed a Perspex phantom comprising a cylinder (height 300 mm, inner diameter 185 mm) fitted with a coaxial inner cylinder (inner diameter 140 mm). The inner cylinder was filled with deionized water doped with copper sulphate (770 mg l−1 CuSO4.5H2O, SigmaAldrich) and sodium chloride (2000 mg l−1 NaCl, Sigma-Aldrich). The outer ring was filled with corn oil (Mazola, 3.4 l). The MR spectrum of corn oil has been shown to contain peaks arising from protons associated with aliphatic (strongest peak at 1.30 ppm) and olefinic (5.31 ppm) components with very similar spectral positions and relative intensities to the main lipid resonances observed in subcutaneous and marrow fat (Kuroda et al 1998, Vigli et al 2003, Wang et al 2009). 2.2. Image acquisition
The phantom and volunteers (1.5 T: seven females; 3 T: three females, one male; BMI range ∼20 to 27) were imaged using 1.5 T (MAGNETOM Avanto, Siemens AG, Healthcare Sector, Erlangen, Germany) and 3 T (Achieva, Philips Healthcare, Best, The Netherlands) MR scanners using protocols, described below, based on previous optimization for abdominal DW-MRI (Kyriazi et al 2011, Padhani et al 2009). The phantom was typically placed on the couch at 45◦ to the z-axis in order to create a large elliptical cross-section in axial images, as found in abdominal imaging (figure 1). The phantom was stored in the scanner room for at least 24 h before scanning in order to stabilize at room temperature (22 ◦ C). The phantom was also scanned at 1.5 T using a Dixon sequence used in abdominal imaging. 1.5 T DW-MRI protocol. Siemens MAGNETOM Avanto, equipped with a work-inprogress EPI package; maximum gradient amplitude 45 mT m−1; anterior body matrix and posterior spine matrix; single-shot EPI; 26 slices; 6 mm slice thickness; no slice gap; axial 2237
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Figure 1. Phantom positioned on couch using body array coil (Avanto, Siemens). The phantom is typically placed at 45◦ to the z-axis in order to create an elliptical crosssection in axial images. Foam wedges have been removed for clarity.
slices; 380 mm × 332 mm FOV; acquired matrix 128 × 112; reconstructed matrix 256; GRAPPA acceleration factor 2; PE direction = AP; TR = 8000–8100 ms; TE = 75–81 ms; b = 0, 100, 500, 900 s mm−2; trace-weighted images; receiver bandwidth 1776 Hz per pixel; NSA = 1; free-breathing; acquisition time = 1 min 44 s (at TR = 8000 ms). Fat suppression was applied using SPAIR, Fat Sat, Water Ex, SSGR and IR (inversion times, TI = 100– 300 ms). Combinations of techniques (Fat Sat + IR and Water Ex + IR (TI = 240 ms)) were also investigated. SSGR is a work-in-progress package on this platform; all other fat suppression techniques used on this platform are available in product sequences. 1.5 T Dixon protocol. Siemens MAGNETOM Avanto; anterior body matrix and posterior spine matrix; 3D VIBE; 22 slices; 5 mm slice thickness; no slice gap; axial slices; 380 mm × 332 mm FOV; acquired matrix 192 × 168; GRAPPA acceleration factor 2; PE direction = AP; TR = 11.7 ms; TE = 2.38 ms and 4.76 ms; receiver bandwidth 491 Hz per pixel; NSA = 1. 3 T DW-MRI protocol. Philips Achieva, equipped with Multi Transmit; software version 3.2.1; maximum gradient amplitude 80 mT m−1; Q-body coil; single-shot EPI; 14 slices; 5 mm slice thickness; no slice gap; axial slices; 380 mm × 344 mm FOV; acquired matrix 128 × 115; reconstructed matrix 256; no parallel imaging; PE direction = AP; TR = 12000 ms; TE = 108 ms; b = 0, 100, 500, 900 s mm−2; gradient overplus; water-fat shift = 32.686 pixels, bandwidth = 13.3 Hz, bandwidth in EPI frequency direction = 2324.6 Hz; NSA = 1; acquisition time = 2 min 24 s. Fat suppression was applied using SPAIR (delay times 140– 220 ms), SPIR, SSGR and IR (TI = 100–400 ms). Combinations of techniques SPAIR + SSGR; IR (TI = 200 ms) + SSGR; and IR (TI = 260 ms) + SSGR) were also investigated. SSGR is a Clinical Science Key on this platform but is available in product sequences on newer platforms; all other fat suppression techniques used on this platform are available in product sequences. The SPAIR delay time was only adjustable on the 3 T scanner used in this study: the optimal value depends on the T1 of the aliphatic fat as well as on the repetition time (TR) and the number of slices (N) in a diffusion-weighted EPI sequence. As all magnetization within 2238
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(a)
(b)
(c) (d)
(e)
(f )
(g)
(h)
Figure 2. Diffusion-weighted images (1.5 T; b = 900 s mm−2) of phantom (top row) and
volunteer (bottom row): (a), (e) without fat suppression; (b), (f) fat suppression applied using IR; (c), (g) fat suppression applied using SPAIR. Aliphatic and olefinic fat signals are marked by open and filled arrows respectively. (d) ROIs used to measure signal intensities in aliphatic fat, olefinic fat, water and background (B) regions in images of phantom. (h) ADC map derived from images of volunteer without fat suppression. The narrow arrow indicates a region of the ADC map which has been corrupted by the overlying signal from chemical-shifted fat.
the range of frequencies selected by the inversion pulse is inverted after every SPAIR TR (time between frequency-selective inversion pulses), the TR is generally not long enough to allow full recovery of the fat magnetisation between each inversion pulse. Therefore, the fat signal as a function of SPAIR delay (TI) can be described at steady state by (1) where T1 is the longitudinal relaxation time of the aliphatic fat: −SPAIR TR −T I + exp (1) S(T I) ∝ 1 − 2 exp T1 T1 The optimal SPAIR delay (TIopt) which nulls the signal from aliphatic fat is described by (2) where ‘SPAIR TR’ has been rewritten to explicitly include the TR of the sequence and the number of slices. Images of the phantom and volunteers were acquired using SPAIR delay times from 140 to 220 ms in order to select the delay times at which the signal from the aliphatic fat was minimized: −TR 1 1 + exp . (2) T Iopt = −T1 loge 2 T1 N
2.3. Image analysis
Inversion delays for IR were adjusted and the strengths of the aliphatic and olefinic components of the fat signal were compared quantitatively in the phantom and qualitatively in the volunteers. Homogeneity of fat and water signals was assessed visually. Quantitative analysis was carried out using regions of interest (ROIs) drawn in the central slices of the b = 900 s mm−2 images, as shown in figure 2, (Matlab 2011, MathWorks Inc., Natick, MA). ROIs were drawn in areas where signals from aliphatic fat, olefinic fat and water appeared separately in the images, taking care to avoid overlying signals from chemical shift and ghosts. 2239
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Figure 3. Signal intensities measured in ROIs in diffusion-weighted images (1.5 T; b =
900 s mm−2) of phantom with fat suppression applied using IR (TI = 100 to 300 ms). Error bars represent standard deviation of pixel values in ROIs.
3. Results Qualitative comparisons of all available methods of fat suppression applied in the phantom are given at 1.5 T in table 1 and 3 T in table 2. At 1.5 T, although SSGR could have been added to any of the other methods we did not pursue this as we found that SSGR was ineffective when applied using our protocol at 1.5 T. At 3 T it was also possible to combine SPIR with SSGR on the scanner used in this study but this combination was not investigated as SPIR showed much poorer fat suppression than SPAIR when the techniques were applied individually. Figure 2 shows diffusion-weighted images (b = 900 s mm−2) of the phantom and a volunteer at 1.5 T. Images were acquired without fat suppression (a), (e) and with fat suppression using IR (b), (f) and SPAIR (c), (g). The images acquired without fat suppression show the signal from the aliphatic component of the fat shifted in the anterior direction (open arrows) and the signal from the olefinic fat shifted in the posterior direction (filled arrows). The images acquired using IR (figures 2(b) and (f)) demonstrate suppression of the aliphatic and olefinic components of the fat signal. The degree of suppression of each component may be controlled by adjusting TI, as shown in figure 3. At 1.5 T the signal from the aliphatic fat was suppressed most effectively when TI = 140 ms and the signal from the olefinic fat was suppressed at TI = 240 ms or greater. The inversion delays for the images shown in figure 2 were selected to optimize suppression of the aliphatic component of the fat signals (140 ms in the phantom and 180 ms in the volunteer). Figures 2 and 3 also demonstrate attenuation of the water signal using IR. Also, the images acquired using SPAIR (figures 2(c) and (g)) show that a spectrally-selective technique suppresses the aliphatic fat signal but does not suppress the olefinic component (filled arrows). A quantitative comparison of fat suppression techniques at 1.5 T is shown in figure 4. Figure 5 shows examples of diffusion-weighted images (b = 900 s mm−2) of the phantom at 3 T. B0-induced distortion of the phantom is observable in the images from the central slice and end slice. The difference in slice positions between central slice and end slice in figure 5 was 42 mm. Inhomogeneity of the water signal is also visible in the images due to the 2240
Suppression of aliphatic fat signal
Suppression of olefinic fat signal
Homogeneity of fat suppression
Attenuation of water signal
SPAIR
Yes (figures 2 and 4)
No (figures 2 and 4)
No (figure 4)
Fat Sat
Yes (figure 4)
No (figure 4)
Water Ex
Yes (figure 4)
No (figure 4)
IR
Optimised using TI = 140 ms in phantom; 180 ms for subcutaneous fat in abdominal images of healthy volunteers. Partial suppression also occurs at other TIs. (figures 2–4) Would not provide adequate fat suppression for body DWMRI using this protocol at 1.5 T. (figure 4) Fat Sat suppresses aliphatic fat; IR suppresses aliphatic and olefinic fat. (figure 4)
Optimised using TI = 240 ms in phantom; 260 ms for subcutaneous fat in abdominal images of healthy volunteers. Partial suppression also occurs at other TIs. (figures 2–4) No (figure 4)
Some unsuppressed fat visible at edges of large FOV. Less homogeneous than SPAIR. Some unsuppressed regions throughout large FOV. Less homogeneous than SPAIR; more homogeneous than Fat Sat. Some unsuppressed regions throughout large FOV. Homogeneous
2241
Method
SSGR
Fat Sat + IR (TI = 240 ms)
Water Ex + IR Water Ex suppresses aliphatic (TI = 240 ms) fat; IR suppresses aliphatic and olefinic fat. (figure 4)
No (figure 4)
Attenuation of all signals, depending on T1 and TI; greater attenuation of water signal at longer inversion times. (figures 2–4) No (figure 4)
Attenuation of all signals using IR; greater attenuation of water signal at longer inversion times. (figure 4) Attenuation of all signals using IR; greater attenuation of water signal at longer inversion times. (figure 4) J M Winfield et al
Homogeneous but poor suppression throughout FOV due to insufficient chemical shift at. this field strength. Long inversion time for IR used to Homogeneous suppression of optimise suppression of signal olefinic fat signal. Some from olefinic fat (240 ms in phantom; unsuppressed regions of aliphatic 260 ms in volunteers). (figure 4) fat throughout large FOV. Long inversion time for IR used to Homogeneous suppression of optimise suppression of signal from olefinic fat signal. Some olefinic fat (240 ms in phantom; unsuppressed regions of aliphatic 260 ms in volunteers). (figure 4) fat at edges of large FOV but more homogeneous than Fat Sat + IR.
No (figure 4)
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Table 1. Summary of phantom experiments at 1.5 T.
2242
Method
Suppression of aliphatic fat signal
Suppression of olefinic fat signal
Homogeneity of fat suppression
Attenuation of water signal
SPAIR
Yes (figure 5)
No (figure 5)
No
SPIR
Yes
No
SSGR
Yes (figure 6)
Some suppression (figure 6)
IR
Optimised using TI = 200 ms in phantom; 220 ms for subcutaneous fat in abdominal images of healthy volunteers. SPAIR and SSGR both suppress aliphatic fat; better suppression when applied together than either technique applied alone. SSGR suppresses aliphatic fat; IR suppresses aliphatic and olefinic fat. (figure 5)
Optimised using TI = 260 ms in phantom and in volunteers.
Inhomogeneous suppression in central slice. Fat suppression fails at edges of FOV in end slices. (figure 5) Inhomogeneous suppression in central slice. Less homogeneous than SPAIR. Poor fat suppression in end slices. Inhomogeneous suppression in central slice. Poor fat suppression at edges of FOV in off-centre slices. (figure 6) Some inhomogeneity in fat suppression throughout large FOV on central slice and end slices. Fat suppression fails at edges of FOV in off-centre slices but is not worse than either technique applied individually.
SPAIR + SSGR
SSGR + IR
SSGR partially suppresses olefinic fat; SPAIR does not suppress olefinic fat signal. Long inversion time for IR used to optimise suppression of signal from olefinic fat (260 ms in phantom and volunteers). (figure 5)
Homogeneous suppression across large FOV in central slice and end slices. (figure 5)
No
Phys. Med. Biol. 59 (2014) 2235
Table 2. Summary of phantom experiments at 3 T.
Attenuation of off-resonant water at edges of large FOV. (figure 6) Attenuation of all signals depending on T1; greater attenuation of water signal at longer inversion times. Attenuation of off-resonant water at edges of large FOV was not different to SSGR applied alone.
J M Winfield et al
Attenuation of water signal when using IR, especially using longer inversion times. Attenuation of off-resonant water at edges of large FOV was not different to SSGR applied alone. (figure 5)
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90 Aliphatic fat Olefinic fat Water
80
Mean signal in ROIs
70 60 50 40 30 20 10 0
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Figure 4. Signal intensities measured in ROIs in diffusion-weighted images (1.5 T; b =
900 s mm−2) of phantom without fat suppression (1) and with fat suppression applied using SPAIR (2), Fat Sat (3), Water Ex (4), IR (TI = 140 ms) (5), IR (TI = 240 ms) (6), SSGR (7), IR (TI = 240 ms) combined with Fat Sat (8) and IR (TI = 240 ms) combined with Water Ex (9).
B1 inhomogeneity observed at 3 T. Inhomogeneity of the water signal was observed with and without Multi Transmit. At 3 T, the most effective suppression of the aliphatic fat signal in the phantom using SPAIR was obtained using a delay time of 180 ms. In volunteers, a SPAIR delay of 200 ms was needed when using the same protocol. This is in good agreement with the delay time calculated using (2) assuming a value of 320 ms for the T1 of the aliphatic component of subcutaneous abdominal fat in volunteers at 3 T. The inhomogeneous suppression of the aliphatic component of the fat signal that was observed using spectrally-selective techniques (in this case SPAIR) is demonstrated in figures 5(a) and (b). The aliphatic fat signal is inhomogeneously suppressed across the large FOV in the central slice and remains unsuppressed at the edge of the FOV in the end slice (open arrows). The olefinic fat signal remains unsuppressed using SPAIR (filled arrows). Figures 5(c) and (d) show homogeneous suppression of aliphatic and olefinic fat signals across the large FOV using IR (TI = 200 ms) combined with SSGR. Attenuation of the water signal is also visible at the edge of the FOV in figure 5(d) due to off-resonant effects. Loss of water signal also occurs at the centre of the phantom due to B1 inhomogeneity. Figure 6 demonstrates attenuation of the water signal at the edge of the FOV when SSGR is applied. Figure 6(a) shows an image acquired without fat suppression while figure 6(b) shows an image of the same slice SSGR applied. The narrow arrow in figure 6(b) highlights the loss of the water signal at the edge of a large FOV, due to off-resonant effects, when SSGR is applied. Figure 6(b) also demonstrates good suppression of the aliphatic fat signal at the centre of the FOV using SSGR but failure of the fat suppression at the edge of the FOV. The olefinic fat signal is partly suppressed using SSGR in the protocol employed in this study at 3 T. Loss of water signal also occurs at the centre of the phantom due to B1 inhomogeneity. Figure 7 shows fat (figure 7(a)) and water (figure 7(b)) images of the phantom derived from a Dixon sequence at 1.5 T. 2243
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(a)
(b)
(c)
(d)
Figure 5. Diffusion-weighted images (3 T; b = 900 s mm−2) of phantom showing (a), (c) central slice and (b), (d) end slice. Note the phantom appears on the left-hand side of the image in the end slice due to the angulation of the phantom in the scanner. (a), (b) Fat suppression was applied using SPAIR (delay time = 180 ms). (c), (d) Fat suppression was applied using IR (TI = 200 ms) combined with SSGR. Window levels and widths have adjusted to demonstrate salient features in each image. Open and filled arrows show unsuppressed signals from aliphatic and olefinic fat, respectively.
4. Discussion We have demonstrated that the images from a specially designed phantom are concordant with results obtained from volunteers at 1.5 T and 3 T and are amenable to quantitative analysis making the phantom an alternative to volunteer imaging in protocol development. 4.1. Spectral properties
Both components of the fat signal observed in images of the phantom and in the volunteers were significantly shifted, for example a shift of 16 pixels in the anterior direction for the aliphatic fat signal in corn oil and in subcutaneous abdominal fat at 1.5 T. The stronger component of the fat signal (the aliphatic fat protons) was shifted in the anterior direction and the weaker component (olefinic fat protons) by a smaller distance in the opposite direction in the phantom and in volunteers. These results confirm that corn oil can be used to produce images that mirror the spectral characteristics of human fat. The low bandwidth of EPI in the PE direction led to large chemical shift artefacts and hence allowed resolution of the aliphatic 2244
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(a)
(b)
Figure 6. Diffusion-weighted images (b = 900 s mm−2) of phantom at 3 T showing end slices of imaging volume. Note the phantom appears on the left-hand side of the image in the end slice due to the angulation of the phantom in the scanner. (a) No fat suppression. (b) Fat suppression applied using SSGR. The arrow shows suppression of off-resonant water in (b). Loss of water signal also occurs at the centre of the phantom due to B1 inhomogeneity. Image contrast has been adjusted to highlight water suppression.
(a)
(b)
Figure 7. Images of (a) fat and (b) water derived from a Dixon sequence at 1.5 T.
and olefinic signals shifted in opposite directions along the PE axis. The signals would not have been resolved in images acquired using conventional (non-EPI) spin-echo or gradient-echo sequences where only a small chemical shift of the aliphatic component of the fat signal in the frequency-encoding direction would be expected. However, EPI sequences are preferred in clinical DW-MRI because of their acquisition speed and hence tolerance of motion. Although up to ten resonances have been resolved in the 1H NMR spectra of subcutaneous fat, marrow fat and corn oil (Kuroda et al 1998, Vigli et al 2003, Ren et al 2008), signals from these individual resonances were not resolved as separate features in the experiments described in this study. Quantitative assessment of fat in the phantom confirmed that the aliphatic fat signal was suppressed using spectrally-selective techniques (SPAIR, Fat Sat, Water Ex) while the water signal and the olefinic fat remained unsuppressed. This indicates that the aliphatic fat resonances in corn oil are located within the narrow-bandwidth RF pulses which SPAIR and Fat Sat use to, respectively, invert or saturate the aliphatic fat protons and that the olefinic fat and water resonances are located outside these frequency-selective RF pulses. Similarly, suppression of the aliphatic fat signal in the phantom using Water Ex shows that the aliphatic fat resonances in corn oil were located outside the narrow-bandwidth RF pulse used to selectively excite water protons and that the water and olefinic fat protons were located within the 2245
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frequency range of the water-selective excitation pulse. The most effective suppression of the aliphatic fat signal at 1.5 T was observed using SPAIR. 4.2. T1 properties
The inversion times used to suppress aliphatic and olefinic components of the fat signal using IR in the phantom were within 20–40 ms of the times used in vivo at 1.5 T and 3 T, indicating that the phantom could be used to optimize inversion times for IR with only small adjustments required for use in vivo. Of the techniques investigated in this study, only IR suppressed the olefinic fat signal. A longer TI was required to achieve this compared to that required for the aliphatic fat signal. However, despite its ability to suppress olefinic fat and provide better performance in inhomogeneous B0 fields, the loss of signal and introduction of T1-weighting renders IR undesirable in some applications. The T1 relaxation time of the doped water in the phantom is ∼400 ms at room temperature at 1.5 T which is considerably shorter than the T1 of many tissues measured in vivo, for example T1 between 1200 and 1800 ms have been reported in solid tumours in the abdomen and pelvis at 1.5 T (O’Connor et al 2009). The water attenuation observed in the phantom therefore represented a worse case than would be expected in vivo where T1s are longer. The optimal SPAIR delay for the protocol used in this study at 3 T was 180 ms in the phantom and 200 ms in volunteers. The phantom, therefore, was suitable for selecting an approximate SPAIR delay and for investigating the efficiency of the SPAIR fat suppression across the FOV. Only a small change in the SPAIR delay was required to adapt the protocol for use in vivo. 4.3. Protocol development
The phantom can be used to test a protocol using all available fat suppression techniques, for example to rule out techniques in the initial stages of development. The use of the phantom reduces the need for volunteers, particularly in the early stages of developing a protocol. The phantom can be used to compare images from different scanners, for example in multi-centre projects, as the phantom avoids the variation in body habitus between volunteers. The phantom does not remove the need for imaging of volunteers when developing a new protocol as it is still important to assess whether a technique provides robust fat suppression in a representative cohort of volunteers. The phantom can be used for quantitative analysis, for example comparison between techniques, provided the coil sensitivities, gain and image scale factors are kept fixed. This was the case in the quantitative experiments discussed in this study as the positions of the phantom, coils and FOV were not changed between acquisitions and the same shim was used in each acquisition. Relative intensities of water and fat signals can also be compared. The phantom has been used for 18 months without noticeable deterioration of its contents nor changes in the properties discussed in this study. Failures in fat suppression at the edges of the FOV at 1.5 T using SPAIR and Fat Sat in the phantom and in volunteers were likely to be due to B0 inhomogeneities where resonant frequencies of the fat protons were shifted outside the range of frequencies included in the spectrally-selective inversion/saturation pulses. More homogeneous fat suppression was achieved using SPAIR than using Fat Sat in the phantom and in volunteers, in agreement with previous results where SPAIR has been shown to be less affected by B0 inhomogeneities than Fat Sat (Kaldoudi et al 1993). 2246
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Fat suppression at 3 T was more challenging than at 1.5 T due to inhomogeneities in the B0 and B1 fields. Combinations of techniques were required to achieve adequate fat suppression across a large FOV at 3 T, as previously demonstrated (Blackledge et al 2010, M¨urtz et al 2012). The size of our phantom was critical for assessing the homogeneity of fat suppression across the large FOV used in abdominal imaging. The effects of B0 inhomogeneities at 3 T were also manifest in the distortion of the elliptical shape of the phantom and suppression of water at the edges of the FOV using SSGR. At 3 T SSGR in combination with IR resulted in good fat suppression across the large FOV employed in this study but attenuation of off-resonant water remained a concern for qualitative and quantitative interpretation of results. The phantom may also be used in development of Dixon protocols for large-FOV imaging. 5. Conclusion We have shown that a large phantom containing corn oil, with a similar cross-section to that found in volunteers in abdominal imaging, is suitable for assessment of spectrally-selective and T1-dependent fat suppression over a large FOV. The phantom may be used for qualitative and quantitative assessments of fat suppression to optimize delay times and to compare techniques applied alone or in combination. It potentially reduces the amount of volunteer imaging required in optimization of protocols, which is particularly relevant when setting up multicentre studies. Combinations of fat suppression techniques provide improved fat suppression at 3 T compared with techniques applied individually: IR combined with SSGR provided the most homogeneous fat suppression across the large FOV. Acknowledgments CRUK BIDD grant C1353/A12762 and CRUK & EPSRC Cancer Imaging Centre in association with MRC and Dept of Health C1060/A10334 and NHS funding to the NIHR Biomedical Research Centre and the Clinical Research Facility in Imaging. Craig Cummings and Nick Smith for building the phantom. Research radiographers and volunteers. We acknowledge the support of the National Institute for Health Research, through the Cancer Research Network (NCRN). We thank Dr Thorsten Feiweier and Dr Berthold Kiefer at Siemens AG for providing the DWI WIP package and Dr David Higgins at Philips Healthcare for providing the SSGR clinical science key. References Blackledge M D, Higgins D, Koh D-M, deSouza N M, Leach M O and Collins D J 2010 Combinatorial fat suppression for diffusion weighted imaging at 3.0 T Proc. Int. Society of Magnetic Resonance in Medicine (Stockholm, Sweden) p 4721 Flask C A, Dale B, Lewin J S and Duerk J L 2003 Radial alternating TE sequence for faster fat suppression Magn. Reson. Med. 50 1095–9 Freed M, de Zwart J A, Loud J T, El Khouli R H, Myers K J, Greene M H, Duyn J H and Badano A 2011 An anthropomorphic phantom for quantitative evaluation of breast MRI Med. Phys. 38 743–53 Gomori J M, Holland G A, Grossman R I, Gefter W B and Lenkinski R E 1988 Fat suppression by section-select gradient reversal on spin-echo MR imaging Radiology 168 493–5 Hernando D, Karampinos D C, King K F, Haldar J P, Majumdar S, Georgiadis J G and Liang Z-P 2011 Removal of olefinic fat chemical shift artifact in diffusion MRI Magn. Reson. Med. 65 692–701 Juan C-J, Chang H-C, Hsueh C-J, Liu H-S, Huang Y-C, Chung H-W, Chen C-Y, Kao H-W and Huang G-S 2009 Salivary glands: echo-planar versus PROPELLER diffusion-weighted MR imaging for assessment of ADCs Radiology 253 144–52 2247
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Kaldoudi E, Williams S C R, Barker G J and Tofts P S 1993 A chemical shift selective inversion recovery sequence for fat-suppressed MRI: theory and experimental validation Magn. Reson. Imaging 11 341–55 Kuroda K, Oshio K, Mulkern R V and Jolesz F A 1998 Optimization of chemical shift selective suppression of fat Magn. Reson. Med. 40 505–10 Kyriazi S, Collins D J, Messiou C, Pennert K, Davidson R L, Giles S L, Kaye S B and deSouza N M 2011 Metastatic ovarian and primary peritoneal cancer: assessing chemotherapy response with diffusion-weighted MR imaging – value of histogram analysis of apparent diffusion coefficients Radiology 261 182–92 Ma J 2008 A single-point Dixon technique for fat-suppressed fast 3D gradient-echo imaging with a flexible echo time J. Magn. Reson. Imaging 27 881–90 Ma J, Singh S K, Kumar A J, Leeds N E and Broemeling L D 2002 Method for efficient fast spin echo Dixon imaging Magn. Reson. Med. 48 1021–7 Ma J, Son J B, Bankson J A, Stafford R J, Choi H and Ragan D 2005 A fast spin echo two-point Dixon technique and its combination with sensitivity encoding for efficient T2-weighted imaging Magn. Reson. Imaging 23 977–82 M¨urtz P, Kaschner M, Tr¨aber F, Kukuk G, Skowasch D, Gieseke J, Schild H H and Willinek W A 2012 Diffusion-weighted whole-body MRI with background body signal suppression: technical improvements at 3.0 T J. Magn. Reson. Imaging 35 456–61 Nagy Z and Weiskopf N 2008 Efficient fat suppression by slice-selection gradient reversal in twicerefocused diffusion encoding Magn. Reson. Med. 60 1256–60 O’Connor J P B et al 2009 Preliminary study of oxygen-enhanced longitudinal relaxation in MRI: a potential novel biomarker of oxygenation changes in solid tumours Int. J. Radiat. Oncol. Biol. Phys. 75 1209–15 Padhani A R et al 2009 Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations Neoplasia 11 102–25 Park H W, Kim D J and Cho Z H 1987 Gradient reversal technique and its applications to chemicalshift-related NMR imaging Magn. Reson. Med. 4 526–36 Ren J, Dimitrov I, Sherry A D and Malloy C R 2008 Composition of adipose tissue and marrow fat in humans by 1H NMR at 7 Tesla J. Lipid Res. 49 2055–62 Rice J R, Milbrandt R H, Madsen E L, Frank G R, Boote E J and Blechinger J C 1998 Anthropomorphic 1 H MRS head phantom Med. Phys. 25 1145–56 Sarlls J E, Pierpaoli C, Talagala S L and Luh W-M 2011 Robust fat suppression at 3T in high-resolution diffusion-weighted single-shot echo-planar imaging of human brain Magn. Reson. Med. 66 1658–65 Vigli G, Philippidis A, Spyros A and Dais P 2003 Classification of edible oils by employing 31P and 1 H NMR spectroscopy in combination with multivariate statistical analysis. A proposal for the detection of seed oil adulteration in virgin olive oils J. Agric. Food Chem. 51 5715–22 Wang L, Salibi N, Wu Y, Schweitzer M E and Regatte R E 2009 Relaxation times of skeletal muscle metabolites at 7T J. Magn. Reson. Imaging 29 1457–64 Wilm B J, Svensson J, Henning A, Pruessmann K P, Boesiger P and Kollias S S 2007 Reduced fieldof-view MRI using outer volume suppression for spinal cord diffusion imaging Magn. Reson. Med. 57 625–30
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Phantom for assessment of fat suppression in large field-of-view diffusion-weighted magnetic resonance imaging
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Institute of Physics and Engineering in Medicine Phys. Med. Biol. 59 (2014) 2235–2248
Physics in Medicine and Biology
doi:10.1088/0031-9155/59/9/2235
Phantom for assessment of fat suppression in large field-of-view diffusion-weighted magnetic resonance imaging J M Winfield 1 , N H M Douglas 1 , N M deSouza 1,2 and D J Collins 1,2 1 CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK 2 Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK
E-mail: [email protected] Received 5 September 2013, revised 6 March 2014 Accepted for publication 21 March 2014 Published 8 April 2014 Abstract
We present the development and application of a phantom for assessment and optimization of fat suppression over a large field-of-view in diffusion-weighted magnetic resonance imaging at 1.5 T and 3 T. A Perspex cylinder (inner diameter 185 mm, height 300 mm) which contains a second cylinder (inner diameter 140 mm) was constructed. The inner cylinder was filled with water doped with copper sulphate and sodium chloride and the annulus was filled with corn oil, which closely matches the spectrum and longitudinal relaxation times of subcutaneous abdominal fat. Placement of the phantom on the couch at 45◦ to the z-axis presented an elliptical cross-section, which was of a similar size and shape to axial abdominal images. The use of a phantom for optimization of fat suppression allowed quantitative comparison between studies without the differences introduced by variability between human subjects. We have demonstrated that the phantom is suitable for selection of inversion delay times, spectral adiabatic inversion recovery delays and assessment of combinatorial methods of fat suppression. The phantom is valuable in protocol development and the assessment of new techniques, particularly in multi-centre trials. Keywords: test object, diffusion-weighted MRI, fat suppression (Some figures may appear in colour only in the online journal)
0031-9155/14/092235+14$33.00
© 2014 Institute of Physics and Engineering in Medicine Printed in the UK & the USA 2235
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1. Introduction Suppression of the signal from fat is essential in diffusion-weighted magnetic resonance imaging (DW-MRI) because qualitative interpretation requires that the overlying signal from unsuppressed chemical-shifted fat does not obscure features of interest in the image and quantitative analysis demands that the superposition of the fat signal on a region of interest does not affect estimation of the apparent diffusion coefficient (ADC). It is also helpful to eliminate fat from the ADC quantification in tissues such as bone marrow, omentum and steatotic liver when assessing malignant infiltration. Fat suppression techniques make use of the differences in the 1H MR spectra of water and fat or their differences in T1 relaxation times, or a combination of the two. The largest peak in the 1H MR spectrum of human fat occurs at 1.30 ppm (referred to here as the aliphatic fat signal since the resonances lie in the aliphatic region of the 1H MR spectrum) and is attributed to protons attached to saturated carbon atoms in CH2 groups together with multiple smaller adjacent peaks (0.90 ppm and 1.59 to 2.77 ppm) (Ren et al 2008). The signal from protons attached to water molecules occurs at 4.7 ppm. Unsuppressed signal from aliphatic fat is shifted relative to the water signal by several pixels in the phase-encode (PE) direction in echo-planar imaging (EPI) at 1.5 T and 3 T. Selective suppression of the aliphatic fat signal by saturation or inversion pulses used in frequency-selective fat suppression techniques, for example fat saturation (Fat Sat), spectral inversion recovery (SPIR) and spectral adiabatic inversion recovery (SPAIR), is therefore possible. Conversely, protons attached to unsaturated carbon atoms have a higher chemical shift than the water protons (5.31 ppm) (Ren et al 2008) and lie outside the narrow-bandwidth radiofrequency (RF) pulses used in spectrally-selective fat suppression techniques. The fat signal at 5.31 ppm will be referred to here as the olefinic fat signal since the resonances lie in the olefinic region of the 1H MR spectrum. The shift of the olefinic fat signal in an image, relative to the water signal, is smaller than the shift of the aliphatic fat signal and occurs in the opposite direction. SPAIR and SPIR use narrow-bandwidth RF pulses to selectively invert the aliphatic fat protons. These techniques use T1 properties in addition to spectral properties to suppress the fat signal making the T1 of the aliphatic fat resonances relevant in optimizing the sequences. Fat Sat uses a non-inverting narrow-bandwidth RF pulse to selectively saturate the aliphatic fat protons. Inhomogeneities in the B0 field that shift some of the aliphatic protons outside the frequency range of selective RF pulses result in imperfect fat suppression in SPAIR, SPIR and Fat Sat. Aliphatic fat resonances may also be suppressed by water-selective excitation (Water Ex) which uses narrow-bandwidth RF pulses to selectively excite the water protons (and also excites the adjacent olefinic fat protons) whilst leaving the aliphatic fat protons unexcited. Slice- selective gradient reversal (SSGR), which exploits the difference in resonant frequencies between on-resonance water protons and other off-resonance species (Park et al 1987, Gomori et al 1988, Nagy and Weiskopf 2008), suppresses aliphatic fat more than olefinic fat due to the larger frequency difference between aliphatic fat and water than between olefinic fat and water. SSGR also attenuates the signal from water protons which have been shifted to frequencies away from the main water resonance due to B0 inhomogeneities. There are therefore several challenges in achieving sequences with optimal suppression of the aliphatic and olefinic fat signals. Ethical considerations and volunteer time limit fat suppression sequence optimization in normal volunteers, which are additionally confounded by the natural variation in body habitus within and between subjects. A phantom provides stability, repeatability and measurement data for qualitative and quantitative comparisons between different fat suppression techniques and scanners. However, inappropriate phantoms may fail to reveal salient features in the 2236
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images, for example small phantoms may not reveal failures in fat suppression arising from inhomogeneities in the B0 field at the edges of a large field-of-view (FOV). Inappropriate choice of material for the fat may also produce poorer or better fat suppression than would be found in vivo due to mismatches between the spectra or T1 relaxation times of the material and human fat. Previous studies have reported results from small fat phantoms developed for protocol development in areas such as breast (Freed et al 2011), salivary glands (Juan et al 2009) and brain (Rice et al 1998). Phantoms have also been used to demonstrate new fat suppression techniques (Flask et al 2003, Hernando et al 2011, Kaldoudi et al 1993, Kuroda et al 1998, Ma et al 2002, 2005, Ma 2008, Nagy and Weiskopf 2008, Sarlls et al 2011, Wilm et al 2007). The purpose of this study therefore was to develop and evaluate a phantom for assessment of fat suppression for body DW-MRI that: (1) occupies a large FOV; (2) has a fat spectrum that matches the positions and relative intensities of the main fat resonances observed in vivo; (3) has longitudinal relaxation times that are closely matched to human fat at 1.5 T and 3 T; (4) is composed of stable, inexpensive and widely available materials; (5) has constituents that provide reasonable coil loading and avoid significant B1 inhomogeneities in order to determine optimal fat suppression protocols at 1.5 T and 3 T. In this study we will use the term ‘suppression’ to refer to the intended (desirable) removal of the fat signal from the images. We will use the term ‘attenuation’ to refer to the unintended or undesirable loss of water signal from the images, for example attenuation of water signal by inversion recovery (IR) or attenuation of off-resonant water by SSGR. 2. Materials and methods 2.1. Phantom construction
We constructed a Perspex phantom comprising a cylinder (height 300 mm, inner diameter 185 mm) fitted with a coaxial inner cylinder (inner diameter 140 mm). The inner cylinder was filled with deionized water doped with copper sulphate (770 mg l−1 CuSO4.5H2O, SigmaAldrich) and sodium chloride (2000 mg l−1 NaCl, Sigma-Aldrich). The outer ring was filled with corn oil (Mazola, 3.4 l). The MR spectrum of corn oil has been shown to contain peaks arising from protons associated with aliphatic (strongest peak at 1.30 ppm) and olefinic (5.31 ppm) components with very similar spectral positions and relative intensities to the main lipid resonances observed in subcutaneous and marrow fat (Kuroda et al 1998, Vigli et al 2003, Wang et al 2009). 2.2. Image acquisition
The phantom and volunteers (1.5 T: seven females; 3 T: three females, one male; BMI range ∼20 to 27) were imaged using 1.5 T (MAGNETOM Avanto, Siemens AG, Healthcare Sector, Erlangen, Germany) and 3 T (Achieva, Philips Healthcare, Best, The Netherlands) MR scanners using protocols, described below, based on previous optimization for abdominal DW-MRI (Kyriazi et al 2011, Padhani et al 2009). The phantom was typically placed on the couch at 45◦ to the z-axis in order to create a large elliptical cross-section in axial images, as found in abdominal imaging (figure 1). The phantom was stored in the scanner room for at least 24 h before scanning in order to stabilize at room temperature (22 ◦ C). The phantom was also scanned at 1.5 T using a Dixon sequence used in abdominal imaging. 1.5 T DW-MRI protocol. Siemens MAGNETOM Avanto, equipped with a work-inprogress EPI package; maximum gradient amplitude 45 mT m−1; anterior body matrix and posterior spine matrix; single-shot EPI; 26 slices; 6 mm slice thickness; no slice gap; axial 2237
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Figure 1. Phantom positioned on couch using body array coil (Avanto, Siemens). The phantom is typically placed at 45◦ to the z-axis in order to create an elliptical crosssection in axial images. Foam wedges have been removed for clarity.
slices; 380 mm × 332 mm FOV; acquired matrix 128 × 112; reconstructed matrix 256; GRAPPA acceleration factor 2; PE direction = AP; TR = 8000–8100 ms; TE = 75–81 ms; b = 0, 100, 500, 900 s mm−2; trace-weighted images; receiver bandwidth 1776 Hz per pixel; NSA = 1; free-breathing; acquisition time = 1 min 44 s (at TR = 8000 ms). Fat suppression was applied using SPAIR, Fat Sat, Water Ex, SSGR and IR (inversion times, TI = 100– 300 ms). Combinations of techniques (Fat Sat + IR and Water Ex + IR (TI = 240 ms)) were also investigated. SSGR is a work-in-progress package on this platform; all other fat suppression techniques used on this platform are available in product sequences. 1.5 T Dixon protocol. Siemens MAGNETOM Avanto; anterior body matrix and posterior spine matrix; 3D VIBE; 22 slices; 5 mm slice thickness; no slice gap; axial slices; 380 mm × 332 mm FOV; acquired matrix 192 × 168; GRAPPA acceleration factor 2; PE direction = AP; TR = 11.7 ms; TE = 2.38 ms and 4.76 ms; receiver bandwidth 491 Hz per pixel; NSA = 1. 3 T DW-MRI protocol. Philips Achieva, equipped with Multi Transmit; software version 3.2.1; maximum gradient amplitude 80 mT m−1; Q-body coil; single-shot EPI; 14 slices; 5 mm slice thickness; no slice gap; axial slices; 380 mm × 344 mm FOV; acquired matrix 128 × 115; reconstructed matrix 256; no parallel imaging; PE direction = AP; TR = 12000 ms; TE = 108 ms; b = 0, 100, 500, 900 s mm−2; gradient overplus; water-fat shift = 32.686 pixels, bandwidth = 13.3 Hz, bandwidth in EPI frequency direction = 2324.6 Hz; NSA = 1; acquisition time = 2 min 24 s. Fat suppression was applied using SPAIR (delay times 140– 220 ms), SPIR, SSGR and IR (TI = 100–400 ms). Combinations of techniques SPAIR + SSGR; IR (TI = 200 ms) + SSGR; and IR (TI = 260 ms) + SSGR) were also investigated. SSGR is a Clinical Science Key on this platform but is available in product sequences on newer platforms; all other fat suppression techniques used on this platform are available in product sequences. The SPAIR delay time was only adjustable on the 3 T scanner used in this study: the optimal value depends on the T1 of the aliphatic fat as well as on the repetition time (TR) and the number of slices (N) in a diffusion-weighted EPI sequence. As all magnetization within 2238
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(a)
(b)
(c) (d)
(e)
(f )
(g)
(h)
Figure 2. Diffusion-weighted images (1.5 T; b = 900 s mm−2) of phantom (top row) and
volunteer (bottom row): (a), (e) without fat suppression; (b), (f) fat suppression applied using IR; (c), (g) fat suppression applied using SPAIR. Aliphatic and olefinic fat signals are marked by open and filled arrows respectively. (d) ROIs used to measure signal intensities in aliphatic fat, olefinic fat, water and background (B) regions in images of phantom. (h) ADC map derived from images of volunteer without fat suppression. The narrow arrow indicates a region of the ADC map which has been corrupted by the overlying signal from chemical-shifted fat.
the range of frequencies selected by the inversion pulse is inverted after every SPAIR TR (time between frequency-selective inversion pulses), the TR is generally not long enough to allow full recovery of the fat magnetisation between each inversion pulse. Therefore, the fat signal as a function of SPAIR delay (TI) can be described at steady state by (1) where T1 is the longitudinal relaxation time of the aliphatic fat: −SPAIR TR −T I + exp (1) S(T I) ∝ 1 − 2 exp T1 T1 The optimal SPAIR delay (TIopt) which nulls the signal from aliphatic fat is described by (2) where ‘SPAIR TR’ has been rewritten to explicitly include the TR of the sequence and the number of slices. Images of the phantom and volunteers were acquired using SPAIR delay times from 140 to 220 ms in order to select the delay times at which the signal from the aliphatic fat was minimized: −TR 1 1 + exp . (2) T Iopt = −T1 loge 2 T1 N
2.3. Image analysis
Inversion delays for IR were adjusted and the strengths of the aliphatic and olefinic components of the fat signal were compared quantitatively in the phantom and qualitatively in the volunteers. Homogeneity of fat and water signals was assessed visually. Quantitative analysis was carried out using regions of interest (ROIs) drawn in the central slices of the b = 900 s mm−2 images, as shown in figure 2, (Matlab 2011, MathWorks Inc., Natick, MA). ROIs were drawn in areas where signals from aliphatic fat, olefinic fat and water appeared separately in the images, taking care to avoid overlying signals from chemical shift and ghosts. 2239
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Figure 3. Signal intensities measured in ROIs in diffusion-weighted images (1.5 T; b =
900 s mm−2) of phantom with fat suppression applied using IR (TI = 100 to 300 ms). Error bars represent standard deviation of pixel values in ROIs.
3. Results Qualitative comparisons of all available methods of fat suppression applied in the phantom are given at 1.5 T in table 1 and 3 T in table 2. At 1.5 T, although SSGR could have been added to any of the other methods we did not pursue this as we found that SSGR was ineffective when applied using our protocol at 1.5 T. At 3 T it was also possible to combine SPIR with SSGR on the scanner used in this study but this combination was not investigated as SPIR showed much poorer fat suppression than SPAIR when the techniques were applied individually. Figure 2 shows diffusion-weighted images (b = 900 s mm−2) of the phantom and a volunteer at 1.5 T. Images were acquired without fat suppression (a), (e) and with fat suppression using IR (b), (f) and SPAIR (c), (g). The images acquired without fat suppression show the signal from the aliphatic component of the fat shifted in the anterior direction (open arrows) and the signal from the olefinic fat shifted in the posterior direction (filled arrows). The images acquired using IR (figures 2(b) and (f)) demonstrate suppression of the aliphatic and olefinic components of the fat signal. The degree of suppression of each component may be controlled by adjusting TI, as shown in figure 3. At 1.5 T the signal from the aliphatic fat was suppressed most effectively when TI = 140 ms and the signal from the olefinic fat was suppressed at TI = 240 ms or greater. The inversion delays for the images shown in figure 2 were selected to optimize suppression of the aliphatic component of the fat signals (140 ms in the phantom and 180 ms in the volunteer). Figures 2 and 3 also demonstrate attenuation of the water signal using IR. Also, the images acquired using SPAIR (figures 2(c) and (g)) show that a spectrally-selective technique suppresses the aliphatic fat signal but does not suppress the olefinic component (filled arrows). A quantitative comparison of fat suppression techniques at 1.5 T is shown in figure 4. Figure 5 shows examples of diffusion-weighted images (b = 900 s mm−2) of the phantom at 3 T. B0-induced distortion of the phantom is observable in the images from the central slice and end slice. The difference in slice positions between central slice and end slice in figure 5 was 42 mm. Inhomogeneity of the water signal is also visible in the images due to the 2240
Suppression of aliphatic fat signal
Suppression of olefinic fat signal
Homogeneity of fat suppression
Attenuation of water signal
SPAIR
Yes (figures 2 and 4)
No (figures 2 and 4)
No (figure 4)
Fat Sat
Yes (figure 4)
No (figure 4)
Water Ex
Yes (figure 4)
No (figure 4)
IR
Optimised using TI = 140 ms in phantom; 180 ms for subcutaneous fat in abdominal images of healthy volunteers. Partial suppression also occurs at other TIs. (figures 2–4) Would not provide adequate fat suppression for body DWMRI using this protocol at 1.5 T. (figure 4) Fat Sat suppresses aliphatic fat; IR suppresses aliphatic and olefinic fat. (figure 4)
Optimised using TI = 240 ms in phantom; 260 ms for subcutaneous fat in abdominal images of healthy volunteers. Partial suppression also occurs at other TIs. (figures 2–4) No (figure 4)
Some unsuppressed fat visible at edges of large FOV. Less homogeneous than SPAIR. Some unsuppressed regions throughout large FOV. Less homogeneous than SPAIR; more homogeneous than Fat Sat. Some unsuppressed regions throughout large FOV. Homogeneous
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Method
SSGR
Fat Sat + IR (TI = 240 ms)
Water Ex + IR Water Ex suppresses aliphatic (TI = 240 ms) fat; IR suppresses aliphatic and olefinic fat. (figure 4)
No (figure 4)
Attenuation of all signals, depending on T1 and TI; greater attenuation of water signal at longer inversion times. (figures 2–4) No (figure 4)
Attenuation of all signals using IR; greater attenuation of water signal at longer inversion times. (figure 4) Attenuation of all signals using IR; greater attenuation of water signal at longer inversion times. (figure 4) J M Winfield et al
Homogeneous but poor suppression throughout FOV due to insufficient chemical shift at. this field strength. Long inversion time for IR used to Homogeneous suppression of optimise suppression of signal olefinic fat signal. Some from olefinic fat (240 ms in phantom; unsuppressed regions of aliphatic 260 ms in volunteers). (figure 4) fat throughout large FOV. Long inversion time for IR used to Homogeneous suppression of optimise suppression of signal from olefinic fat signal. Some olefinic fat (240 ms in phantom; unsuppressed regions of aliphatic 260 ms in volunteers). (figure 4) fat at edges of large FOV but more homogeneous than Fat Sat + IR.
No (figure 4)
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Table 1. Summary of phantom experiments at 1.5 T.
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Method
Suppression of aliphatic fat signal
Suppression of olefinic fat signal
Homogeneity of fat suppression
Attenuation of water signal
SPAIR
Yes (figure 5)
No (figure 5)
No
SPIR
Yes
No
SSGR
Yes (figure 6)
Some suppression (figure 6)
IR
Optimised using TI = 200 ms in phantom; 220 ms for subcutaneous fat in abdominal images of healthy volunteers. SPAIR and SSGR both suppress aliphatic fat; better suppression when applied together than either technique applied alone. SSGR suppresses aliphatic fat; IR suppresses aliphatic and olefinic fat. (figure 5)
Optimised using TI = 260 ms in phantom and in volunteers.
Inhomogeneous suppression in central slice. Fat suppression fails at edges of FOV in end slices. (figure 5) Inhomogeneous suppression in central slice. Less homogeneous than SPAIR. Poor fat suppression in end slices. Inhomogeneous suppression in central slice. Poor fat suppression at edges of FOV in off-centre slices. (figure 6) Some inhomogeneity in fat suppression throughout large FOV on central slice and end slices. Fat suppression fails at edges of FOV in off-centre slices but is not worse than either technique applied individually.
SPAIR + SSGR
SSGR + IR
SSGR partially suppresses olefinic fat; SPAIR does not suppress olefinic fat signal. Long inversion time for IR used to optimise suppression of signal from olefinic fat (260 ms in phantom and volunteers). (figure 5)
Homogeneous suppression across large FOV in central slice and end slices. (figure 5)
No
Phys. Med. Biol. 59 (2014) 2235
Table 2. Summary of phantom experiments at 3 T.
Attenuation of off-resonant water at edges of large FOV. (figure 6) Attenuation of all signals depending on T1; greater attenuation of water signal at longer inversion times. Attenuation of off-resonant water at edges of large FOV was not different to SSGR applied alone.
J M Winfield et al
Attenuation of water signal when using IR, especially using longer inversion times. Attenuation of off-resonant water at edges of large FOV was not different to SSGR applied alone. (figure 5)
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90 Aliphatic fat Olefinic fat Water
80
Mean signal in ROIs
70 60 50 40 30 20 10 0
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Figure 4. Signal intensities measured in ROIs in diffusion-weighted images (1.5 T; b =
900 s mm−2) of phantom without fat suppression (1) and with fat suppression applied using SPAIR (2), Fat Sat (3), Water Ex (4), IR (TI = 140 ms) (5), IR (TI = 240 ms) (6), SSGR (7), IR (TI = 240 ms) combined with Fat Sat (8) and IR (TI = 240 ms) combined with Water Ex (9).
B1 inhomogeneity observed at 3 T. Inhomogeneity of the water signal was observed with and without Multi Transmit. At 3 T, the most effective suppression of the aliphatic fat signal in the phantom using SPAIR was obtained using a delay time of 180 ms. In volunteers, a SPAIR delay of 200 ms was needed when using the same protocol. This is in good agreement with the delay time calculated using (2) assuming a value of 320 ms for the T1 of the aliphatic component of subcutaneous abdominal fat in volunteers at 3 T. The inhomogeneous suppression of the aliphatic component of the fat signal that was observed using spectrally-selective techniques (in this case SPAIR) is demonstrated in figures 5(a) and (b). The aliphatic fat signal is inhomogeneously suppressed across the large FOV in the central slice and remains unsuppressed at the edge of the FOV in the end slice (open arrows). The olefinic fat signal remains unsuppressed using SPAIR (filled arrows). Figures 5(c) and (d) show homogeneous suppression of aliphatic and olefinic fat signals across the large FOV using IR (TI = 200 ms) combined with SSGR. Attenuation of the water signal is also visible at the edge of the FOV in figure 5(d) due to off-resonant effects. Loss of water signal also occurs at the centre of the phantom due to B1 inhomogeneity. Figure 6 demonstrates attenuation of the water signal at the edge of the FOV when SSGR is applied. Figure 6(a) shows an image acquired without fat suppression while figure 6(b) shows an image of the same slice SSGR applied. The narrow arrow in figure 6(b) highlights the loss of the water signal at the edge of a large FOV, due to off-resonant effects, when SSGR is applied. Figure 6(b) also demonstrates good suppression of the aliphatic fat signal at the centre of the FOV using SSGR but failure of the fat suppression at the edge of the FOV. The olefinic fat signal is partly suppressed using SSGR in the protocol employed in this study at 3 T. Loss of water signal also occurs at the centre of the phantom due to B1 inhomogeneity. Figure 7 shows fat (figure 7(a)) and water (figure 7(b)) images of the phantom derived from a Dixon sequence at 1.5 T. 2243
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(a)
(b)
(c)
(d)
Figure 5. Diffusion-weighted images (3 T; b = 900 s mm−2) of phantom showing (a), (c) central slice and (b), (d) end slice. Note the phantom appears on the left-hand side of the image in the end slice due to the angulation of the phantom in the scanner. (a), (b) Fat suppression was applied using SPAIR (delay time = 180 ms). (c), (d) Fat suppression was applied using IR (TI = 200 ms) combined with SSGR. Window levels and widths have adjusted to demonstrate salient features in each image. Open and filled arrows show unsuppressed signals from aliphatic and olefinic fat, respectively.
4. Discussion We have demonstrated that the images from a specially designed phantom are concordant with results obtained from volunteers at 1.5 T and 3 T and are amenable to quantitative analysis making the phantom an alternative to volunteer imaging in protocol development. 4.1. Spectral properties
Both components of the fat signal observed in images of the phantom and in the volunteers were significantly shifted, for example a shift of 16 pixels in the anterior direction for the aliphatic fat signal in corn oil and in subcutaneous abdominal fat at 1.5 T. The stronger component of the fat signal (the aliphatic fat protons) was shifted in the anterior direction and the weaker component (olefinic fat protons) by a smaller distance in the opposite direction in the phantom and in volunteers. These results confirm that corn oil can be used to produce images that mirror the spectral characteristics of human fat. The low bandwidth of EPI in the PE direction led to large chemical shift artefacts and hence allowed resolution of the aliphatic 2244
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(a)
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Figure 6. Diffusion-weighted images (b = 900 s mm−2) of phantom at 3 T showing end slices of imaging volume. Note the phantom appears on the left-hand side of the image in the end slice due to the angulation of the phantom in the scanner. (a) No fat suppression. (b) Fat suppression applied using SSGR. The arrow shows suppression of off-resonant water in (b). Loss of water signal also occurs at the centre of the phantom due to B1 inhomogeneity. Image contrast has been adjusted to highlight water suppression.
(a)
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Figure 7. Images of (a) fat and (b) water derived from a Dixon sequence at 1.5 T.
and olefinic signals shifted in opposite directions along the PE axis. The signals would not have been resolved in images acquired using conventional (non-EPI) spin-echo or gradient-echo sequences where only a small chemical shift of the aliphatic component of the fat signal in the frequency-encoding direction would be expected. However, EPI sequences are preferred in clinical DW-MRI because of their acquisition speed and hence tolerance of motion. Although up to ten resonances have been resolved in the 1H NMR spectra of subcutaneous fat, marrow fat and corn oil (Kuroda et al 1998, Vigli et al 2003, Ren et al 2008), signals from these individual resonances were not resolved as separate features in the experiments described in this study. Quantitative assessment of fat in the phantom confirmed that the aliphatic fat signal was suppressed using spectrally-selective techniques (SPAIR, Fat Sat, Water Ex) while the water signal and the olefinic fat remained unsuppressed. This indicates that the aliphatic fat resonances in corn oil are located within the narrow-bandwidth RF pulses which SPAIR and Fat Sat use to, respectively, invert or saturate the aliphatic fat protons and that the olefinic fat and water resonances are located outside these frequency-selective RF pulses. Similarly, suppression of the aliphatic fat signal in the phantom using Water Ex shows that the aliphatic fat resonances in corn oil were located outside the narrow-bandwidth RF pulse used to selectively excite water protons and that the water and olefinic fat protons were located within the 2245
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frequency range of the water-selective excitation pulse. The most effective suppression of the aliphatic fat signal at 1.5 T was observed using SPAIR. 4.2. T1 properties
The inversion times used to suppress aliphatic and olefinic components of the fat signal using IR in the phantom were within 20–40 ms of the times used in vivo at 1.5 T and 3 T, indicating that the phantom could be used to optimize inversion times for IR with only small adjustments required for use in vivo. Of the techniques investigated in this study, only IR suppressed the olefinic fat signal. A longer TI was required to achieve this compared to that required for the aliphatic fat signal. However, despite its ability to suppress olefinic fat and provide better performance in inhomogeneous B0 fields, the loss of signal and introduction of T1-weighting renders IR undesirable in some applications. The T1 relaxation time of the doped water in the phantom is ∼400 ms at room temperature at 1.5 T which is considerably shorter than the T1 of many tissues measured in vivo, for example T1 between 1200 and 1800 ms have been reported in solid tumours in the abdomen and pelvis at 1.5 T (O’Connor et al 2009). The water attenuation observed in the phantom therefore represented a worse case than would be expected in vivo where T1s are longer. The optimal SPAIR delay for the protocol used in this study at 3 T was 180 ms in the phantom and 200 ms in volunteers. The phantom, therefore, was suitable for selecting an approximate SPAIR delay and for investigating the efficiency of the SPAIR fat suppression across the FOV. Only a small change in the SPAIR delay was required to adapt the protocol for use in vivo. 4.3. Protocol development
The phantom can be used to test a protocol using all available fat suppression techniques, for example to rule out techniques in the initial stages of development. The use of the phantom reduces the need for volunteers, particularly in the early stages of developing a protocol. The phantom can be used to compare images from different scanners, for example in multi-centre projects, as the phantom avoids the variation in body habitus between volunteers. The phantom does not remove the need for imaging of volunteers when developing a new protocol as it is still important to assess whether a technique provides robust fat suppression in a representative cohort of volunteers. The phantom can be used for quantitative analysis, for example comparison between techniques, provided the coil sensitivities, gain and image scale factors are kept fixed. This was the case in the quantitative experiments discussed in this study as the positions of the phantom, coils and FOV were not changed between acquisitions and the same shim was used in each acquisition. Relative intensities of water and fat signals can also be compared. The phantom has been used for 18 months without noticeable deterioration of its contents nor changes in the properties discussed in this study. Failures in fat suppression at the edges of the FOV at 1.5 T using SPAIR and Fat Sat in the phantom and in volunteers were likely to be due to B0 inhomogeneities where resonant frequencies of the fat protons were shifted outside the range of frequencies included in the spectrally-selective inversion/saturation pulses. More homogeneous fat suppression was achieved using SPAIR than using Fat Sat in the phantom and in volunteers, in agreement with previous results where SPAIR has been shown to be less affected by B0 inhomogeneities than Fat Sat (Kaldoudi et al 1993). 2246
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Fat suppression at 3 T was more challenging than at 1.5 T due to inhomogeneities in the B0 and B1 fields. Combinations of techniques were required to achieve adequate fat suppression across a large FOV at 3 T, as previously demonstrated (Blackledge et al 2010, M¨urtz et al 2012). The size of our phantom was critical for assessing the homogeneity of fat suppression across the large FOV used in abdominal imaging. The effects of B0 inhomogeneities at 3 T were also manifest in the distortion of the elliptical shape of the phantom and suppression of water at the edges of the FOV using SSGR. At 3 T SSGR in combination with IR resulted in good fat suppression across the large FOV employed in this study but attenuation of off-resonant water remained a concern for qualitative and quantitative interpretation of results. The phantom may also be used in development of Dixon protocols for large-FOV imaging. 5. Conclusion We have shown that a large phantom containing corn oil, with a similar cross-section to that found in volunteers in abdominal imaging, is suitable for assessment of spectrally-selective and T1-dependent fat suppression over a large FOV. The phantom may be used for qualitative and quantitative assessments of fat suppression to optimize delay times and to compare techniques applied alone or in combination. It potentially reduces the amount of volunteer imaging required in optimization of protocols, which is particularly relevant when setting up multicentre studies. Combinations of fat suppression techniques provide improved fat suppression at 3 T compared with techniques applied individually: IR combined with SSGR provided the most homogeneous fat suppression across the large FOV. Acknowledgments CRUK BIDD grant C1353/A12762 and CRUK & EPSRC Cancer Imaging Centre in association with MRC and Dept of Health C1060/A10334 and NHS funding to the NIHR Biomedical Research Centre and the Clinical Research Facility in Imaging. Craig Cummings and Nick Smith for building the phantom. Research radiographers and volunteers. We acknowledge the support of the National Institute for Health Research, through the Cancer Research Network (NCRN). We thank Dr Thorsten Feiweier and Dr Berthold Kiefer at Siemens AG for providing the DWI WIP package and Dr David Higgins at Philips Healthcare for providing the SSGR clinical science key. References Blackledge M D, Higgins D, Koh D-M, deSouza N M, Leach M O and Collins D J 2010 Combinatorial fat suppression for diffusion weighted imaging at 3.0 T Proc. Int. Society of Magnetic Resonance in Medicine (Stockholm, Sweden) p 4721 Flask C A, Dale B, Lewin J S and Duerk J L 2003 Radial alternating TE sequence for faster fat suppression Magn. Reson. Med. 50 1095–9 Freed M, de Zwart J A, Loud J T, El Khouli R H, Myers K J, Greene M H, Duyn J H and Badano A 2011 An anthropomorphic phantom for quantitative evaluation of breast MRI Med. Phys. 38 743–53 Gomori J M, Holland G A, Grossman R I, Gefter W B and Lenkinski R E 1988 Fat suppression by section-select gradient reversal on spin-echo MR imaging Radiology 168 493–5 Hernando D, Karampinos D C, King K F, Haldar J P, Majumdar S, Georgiadis J G and Liang Z-P 2011 Removal of olefinic fat chemical shift artifact in diffusion MRI Magn. Reson. Med. 65 692–701 Juan C-J, Chang H-C, Hsueh C-J, Liu H-S, Huang Y-C, Chung H-W, Chen C-Y, Kao H-W and Huang G-S 2009 Salivary glands: echo-planar versus PROPELLER diffusion-weighted MR imaging for assessment of ADCs Radiology 253 144–52 2247
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