Background
Methods
Definitions
Collaboration process
Phantom design
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Tubes had to be a minimum of 20 mm diameter so regions of interest (arbitrarily set to13 mm) would exclude in-plane imaging artifacts at the boundaries between tubes related to the use of clinical T1mapping protocols with coarse image resolution, mostly based on single-shot imaging (e.g. Gibbs artifact at the edge of tubes [Fig. 2d] or the potential impact of filtering against it applied differently by various protocol parameters). Altering protocols to optimise phantom scanning would be inconsistent with the aim of the project. The true resolution achieved is further convoluted by the use of asymmetric frequency-encoded readouts for faster repetition time (TR) in balanced steady-state free precession (bSSFP) imaging or partial-phase-encode sampling for shorter total shot duration, and to some extent also by signal variation during the shot.
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Embedding tubes into a gel-filled phantom is important for three reasons: 1) to permit sufficient signal for scanner calibrations; 2) to minimise B 0 and B 1 field distortions local to each tube; and 3) for greater thermal stability. However, embedding all the 13 tubes (to cover 1.5 T and 3 T values) into a single phantom (whether water or water-based gel-filled) will have increased its overall dimensions making it harder to make (our tests and others [7, 8] show that B 1 homogeneity across large ROIs could not be achieved especially at 3 T). Alternative oil-based phantoms have a smaller dielectric permittivity, useful for weaker radiofrequency (RF) displacement current distortion of B 1, but the chemical shift of the matrix fill would require embedded tubes also to use oil-based chemistry (as in diffusion phantoms). Alkanes or similar [9] could not deliver the required range of T1 and T2 (written as T1|T2) and a predominately single-peak nuclear magnetic resonance (NMR) spectrum, with the required temperature stability. By using separate water-based gel-filled phantoms for 1.5 T and 3 T with the known high permittivity of water, at a size large enough to fit the needed tubes there was still significant B 1 distortion (range of different flip angles achieved for a prescribed protocol nominal flip-angle) but we were able to counteract it using a method described later.
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This project aims to provide quality assurance for clinically used T1 protocols without adapting to the phantom (e.g. no switching to spoiled-gradient echo, or using shorter-TR, no alterations of resolution or field of view etc.; see Additional file 1). Clinical T1 mapping protocols are sensitive to off-resonance effects for various well-known reasons. Therefore, B 0distortion near any of the tubes needed to be minimised (tests showed how tube alignment with the B 0 direction was best—this data not shown).
Phantom materials
Design factor | Explanation | Our proposed solution |
---|---|---|
Bottle magnetostatics and B
0
distortion | The ideal phantom would be uniform and ellipsoidal to avoid susceptibility-induced magnetostatic field perturbation. Such a phantom would permit sphere of Lorentz uniformity but this is not easily mass produced. Many phantoms are cylindrical with the long axis along the static field, B
0 but there is usually off-resonance at the z-ends of such objects [7]. | An outer phantom body with a smooth surface and soft rounded-edges, placed inside B
0 still distorts some of the imposed magnetic field lines at its z-ends so we prescribed scanning halfway along the length of the bottle. |
Long term gel stability and risk of moulding | Phantoms with long-term stability could assure the stability of methods applied to patients against scanner alternations and across multiple centers. | Moulding was prevented by aseptic manufacturing, the toxicity of Ni2+ ions, and the absence of nutrients in the type of agarose used. Tap water might contain microbial contamination and metal ions so high purity water was used. The main risk is from contraction of gel on loss of water leading to gaps and water condensation but NiCl2-doped agarose gel phantoms can be stable over a 1-year period [17]. |
Seal, leakages, air trapping for aqueous fill | Air pockets in the agarose gel phantom will give rise to susceptibility artifacts on account of the large mismatch in static magnetic susceptibility between air and surrounding gel producing a local distortion in magnetic field strength. | The main phantom was sealed by a black polypropylene screw cap fitted with a polyethylene foam insert. Each internal digestive tube was sealed by a tight screw cap. Gel preparation with warm, degassed water reduced air bubble formation. Note the tube “base-upward” setting procedure and subsequent “top-up” of the contracted gel in each tube after setting, described in the text. |
Adjustments of B
0 and reference frequency | Adjustments of B
0 and scanner reference frequency over the phantom have the ability to impact T1estimates. | We specified a constant shim volume for each scan. This is manufacturer-dependent—see the T1MES manual [23]. Consistency between repeat scans is the main point. |
Gel diamagnetism | In the T1MES model system, because the impact of the paramagnetic ions is so small, we can conceptually treat the main phantom box as if it had no tubes, as if it were just filled with uniform gel throughout | The T1MES system has partly paramagnetic and partly diamagnetic constituents, but the impact of the paramagnetic Ni2+ ions is small, around 10 % (because concentrations are small) so the overall interaction is diamagnetic, considering the ~9 parts per million diamagnetism of most tissues relative to air from Lenz electronic diamagnetism. |
Gibbs artifact ringing and other inplane effects | Truncating artifacts appear as lines of alternating brightness and darkness in the read-out and phase encode direction. Some effects also from asymmetric readout and ky coverage. | Large diameter digestive tubes to house the 9 agarose doped solutions, so that central regions of each tube are sufficiently distant (a number of pixels away) from regions impacted by artifacts from abrupt signal intensity transitions at the tube edges. |
1.4 T, 1.5 T, 3 T performance | Many paramagnetic relaxation modifiers, including Mn2+ and Cu2+, exhibit significant frequency dependence. | We used Ni2+[13]. |
T1|T2 ranges: blood/myocardium, pre/post-GBCA | The T1|T2 values were carefully modelled for native and post-gadolinium based contrast agent, blood and myocardium. | 5 common tubes, 4 tubes specific to 1.5 T, 4 tubes specific to 3 T. There was no macromolecular addition (no magnetisation transfer modelling) [22]. |
Tube arrangement | The phantom corners are more prone to inhomogeneities of the B
0 and B
1 magnetic fields. | Longer T1 tubes were placed nearer the middle of the phantom layout and avoided the corners. |
Characterization of T1 and T2 dependence on agarose and nickel
B0 uniformity
B1 uniformity
Description target (Tube ID) | T1 (ms at 1.4 Ta) | T2 (ms at 1.4 Ta) | Agarose (%) | NiCl2 (mM) |
---|---|---|---|---|
“Short” post-GBCA blood (A) | 256 | 172 | 0.244 | 5.547 |
“Normal” native blood 1.5 T (B) | 1490 | 282 | 0.373 | 0.362 |
“Long” post-GBCA blood (C) | 427 | 212 | 0.325 | 2.860 |
“Short” native myocardium 1.5 T (D) | 818 | 54 | 2.214 | 1.231 |
“Long” native myocardium 1.5 T (E) | 1384 | 57 | 2.279 | 0.461 |
“Medium” native myocardium 1.5 T (F) | 1107 | 56 | 2.256 | 0.725 |
“Short” post-GBCA myocardium (G) | 295 | 50 | 2.174 | 4.510 |
“Long” post-GBCA myocardium (H) | 557 | 51 | 2.377 | 2.103 |
“Medium” post-GBCA myocardium (I) | 429 | 50 | 2.306 | 2.942 |
“Normal” native blood 3 T (J) | 1870 | 288 | 0.388 | 0.180 |
“Short” native myocardium 3 T (K) | 1043 | 56 | 2.245 | 0.858 |
“Long” native myocardium 3 T (L)
| 1510 | 55 | 2.289 | 0.342 |
“Medium” native myocardium 3 T (M) | 1279 | 56 | 2.273 | 0.531 |
Outer matrix gel fill | 846 | 141 | 0.780 | 1.155 |
Temperature dependence of T1 and T2
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Test 1: Performed at the PTB laboratory in June 2015 on a 3 T prototype-D (whole phantom with 9 tubes) across 17 temperatures between 14.9 °C and 32.0 °C for T1 and across 6 temperatures between 15.6 °C and 31.1 °C for T2. Each measurement was repeated twice (with a 2 day gap) and made using a 3 T Siemens Magnetom Verio system (VB17) and a 12-channel head coil.
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Test 2: Performed at the NIST laboratory in November 2015 on six loose tubes from the final production run of E-model phantoms. T1|T2 were measured at 9.9, 17.1, 20.1, 23.1 and 30.1 °C on an Agilent 1.5 T small bore scanner in a temperature-controlled environment. Temperatures were measured using a fiber optic probe. T1 was measured by inversion-recovery spin echo (IRSE) (TR [s] = 10, inversion time [TI, ms] = 50, 75, 100, 125, 150, 250, 500, 1000, 1500, 2000, 3000) and T2 by SE (TR [s] = 10, TE [echo time, ms] = 15, 30, 60, 120, 240, 480, 960). Note that some of the data acquired under short-term reproducibility was obtained in support of temperature Test 2.
Short-term reproducibility
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Test 1: Six loose tubes from the final production run of E-model phantoms were tested for short-term reproducibility of T1|T2 values at the NIST laboratory in November 2015, at 20.1 °C on an Agilent 1.5 T small bore scanner. T1 was measured by IRSE (TR [s] = 10, TE [ms] = 14.75, TI [ms] = 50, 75, 100, 125, 150, 250, 500, 1000, 1500, 2000, 3000) and T2 by SE (TR [s] =10, TE [ms] =14.75, 20, 40, 80, 160).
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Test 2: One of the final E-model phantoms for 3 T was tested for short-term repeatability of T1|T2 values using a Siemens 3 T Skyra at Royal Brompton Hospital in November 2015. This test was performed by removing and repositioning the receiver coil, phantom and its supports on each of ten runs, incurring full readjustment of all scanner setup procedures before each run. The acquired data was ten runs, each containing two repeated T1 maps, performed at 20.3 ± 0.5 °C. An extension of this work showed that the temperature increase of the T1MES phantom caused by specific absorption rate (SAR) deposition during imaging for repeated T1 maps was negligible.
Detailed construction of phantoms
Prototype and production batch testing and quality control
Scanning protocol for T1MES
Statistics
Results
Model predictions of T1 and T2
Reference T1 and T2 values
B0 uniformity
B1 uniformity
Temperature dependency experiments
Short-term reproducibility
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Test 1: Six loose tubes as used in the 1.5 T E-model (Fig. 9) showed a CoV of ≤1 % for both T1 and T2reproducibility. Tube B with the longest T1 and T2 showed the greatest variability between repeated scans.×
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Test 2: Test-retest evaluation of one of the final phantoms for 3 T by cardiac T1 mapping, including complete repositioning and readjustments, also gave a short-term repeatability CoV for T1 ≤1 % (Table 3 detailing results for 3 T). For T2 measured by fast T2-prepared single-shot methods, the CoV was usually below 1 % with an exceptionally large 4.1 % in the tube B with longest T1.Table 3Short-term reproducibility experiments in a 3 T final phantom (E-model)*TubeParameterSequenceCoV (%)Mean diff. ± s.d.AT1pre_MOLLI_5(3)3_256_T10.16255 ± 0.4post_MOLLI_4(1)3(1)2_256_MOCO_T10.18255 ± 0.5T2T2_4pt_TRUFI_192i_T20.66194 ± 1.3T2_4pt_GRE_192i_T20.61134 ± 0.8JT1pre_MOLLI_5(3)3_256_T10.141860 ± 2.6post_MOLLI_4(1)3(1)2_256_MOCO_T10.171672 ± 2.8T2T2_4pt_TRUFI_192i_T24.06227 ± 9.2T2_4pt_GRE_192i_T21.37203 ± 2.8CT1pre_MOLLI_5(3)3_256_T10.08460 ± 0.4post_MOLLI_4(1)3(1)2_256_MOCO_T10.08461 ± 0.4T2T2_4pt_TRUFI_192i_T20.52195 ± 1.0T2_4pt_GRE_192i_T20.76160 ± 1.2KT1pre_MOLLI_5(3)3_256_T10.13953 ± 1.2post_MOLLI_4(1)3(1)2_256_MOCO_T10.10917 ± 0.9T2T2_4pt_TRUFI_192i_T20.9860 ± 0.6T2_4pt_GRE_192i_T20.6749 ± 0.3LT1pre_MOLLI_5(3)3_256_T10.081372 ± 1.1post_MOLLI_4(1)3(1)2_256_MOCO_T10.161252 ± 2.0T2T2_4pt_TRUFI_192i_T20.9156 ± 0.5T2_4pt_GRE_192i_T20.8949 ± 0.4MT1pre_MOLLI_5(3)3_256_T10.151178 ± 1.8post_MOLLI_4(1)3(1)2_256_MOCO_T10.121104 ± 1.3T2T2_4pt_TRUFI_192i_T20.9158 ± 0.5T2_4pt_GRE_192i_T20.6649 ± 0.3GT1pre_MOLLI_5(3)3_256_T10.19285 ± 0.6post_MOLLI_4(1)3(1)2_256_MOCO_T10.20285 ± 0.6T2T2_4pt_TRUFI_192i_T20.2986 ± 0.2T2_4pt_GRE_192i_T21.0249 ± 0.5HT1pre_MOLLI_5(3)3_256_T10.11527 ± 0.6post_MOLLI_4(1)3(1)2_256_MOCO_T10.09527 ± 0.5T2T2_4pt_TRUFI_192i_T20.3566 ± 0.2T2_4pt_GRE_192i_T20.7246 ± 0.3IT1pre_MOLLI_5(3)3_256_T10.06406 ± 0.3post_MOLLI_4(1)3(1)2_256_MOCO_T10.05409 ± 0.2T2T2_4pt_TRUFI_192i_T20.2172 ± 0.2T2_4pt_GRE_192i_T20.1947 ± 0.1
Production, distribution and initiation of trial
Center | Magnet characteristics | ||||||
---|---|---|---|---|---|---|---|
Vendor | Tesla | Name | YOM | Software | Boreb (cm) | Gradient performancec
| |
St Thomas’ Hospital UK | Siemens | 1.5 | Aera | 2015 | VE11 | 70 | 45/200 |
St Thomas’ Hospital UK | Philips | 1.5 | Ingenia | 2013 | R4.1.3SP2 | 70 | 33/200 |
Oslo University Hospital Norway | Siemens | 1.5 | Aera | 2014 | VE11 | 70 | 40/200 |
Bristol Heart Institute UK | Siemens | 1.5 | Avanto | 2009 | VB17A | 60 | 44/180 |
Diagnostikum Berlin Germany | Siemens | 1.5 | Aera | 2015 | VE11 | 70 | 45/200 |
GOSH UK | Siemens | 1.5 | Avanto | 2007 | VB17 | 60 | 40/180 |
NIH Bethesda US | Siemens | 1.5 | Aera | 2014 | VE11 | 70 | 45/200 |
Pittsburgh Pennsylvania US | Siemens | 1.5 | Espree | 2009 | VB17A | 70 | 40/200 |
Leiden UMC The Netherlands | Philips | 1.5 | Ingenia | 2014 | R5.1.7SP2 | 70 | 45/200 |
Leeds General Infirmary UK | Philips | 1.5 | Ingenia | 2014 | R5.1.7SP2 | 70 | 45/200 |
MUMC The Netherlands | Philips | 1.5 | Ingenia | 2012 | R 5.1.7SP2 | 70 | 45/200 |
Policlinico San Donato Italy | Siemens | 1.5 | Aera | 2012 | VD13A | 70 | 45/200 |
Papworth UK | Siemens | 1.5 | Avanto | 2008 | VB17A | 60 | 50/200 |
Wythenshawe Manchester UK | Siemens | 1.5 | Avanto | 2008 | VB17A | 60 | 45/200 |
Copenhagen University Hospital Denmark | Siemens | 1.5 | Avanto | 2008 | VD13A | 60 | 45/200 |
Queen Elizabeth Hospital Birmingham UK | Siemens | 1.5 | Avanto | 2008 | VB17A | 60 | 33/125 |
Birmingham Children’s Hospital UK | Siemens | 1.5 | Avanto | 2010 | VB17A | 60 | 33/125 |
University of Kentucky USA | Siemens | 1.5 | Aera | 2012 | VD13A | 70 | 45/200 |
Charles Perkins Sydney Australia | Siemens | 1.5 | Avanto | 2013 | VE17A | 70 | 45/200 |
Taichung Veterans Hospital Taiwan | Siemens | 1.5 | Aera | 2005 | VE11 | 60 | 45/200 |
Monash Heart Australia | Siemens | 1.5 | Avanto | 2010 | VB17 | 55 | 40/200 |
Niguarda Hospital Milan Italy | Siemens | 1.5 | Avanto | 2005 | VB17A | 60 | 40/200 |
Golden Jubilee Glasgow UK | Siemens | 1.5 | Avanto | 2008 | VB17A | 60 | 45/200 |
T-T!ME Multi-center phantoma
| |||||||
INSERM U1044 France | Siemens | Aera | 2012 | VD13A | 70 | 40/200 | |
King Abdul-Aziz Saudi Arabia | GE | 1.5 | Discovery MR450 | 2012 | DV24 | 60 | 50/200 |
Prince Charles Hospital Queensland | Siemens | 1.5 | Aera | 2011 | VD13A | 70 | 45/200 |
Federal Medical Center Moscow | GE | 1.5 | Optima MR450w | 2014 | DV25 | 70 | 44/200 |
Medical University of Vienna Austria | Siemens | 1.5 | Avanto | 2006 | VD13B | 60 | 40/200 |
DHZ Berlin Germany | Philips | 1.5 | Achieva | 2008 | R5.1.8 | 60 | 33/180 |
St George’s University London UK | Siemens | 1.5 | Aera | 2014 | E11 | 70 | 45/200 |
RBHT London UK | Siemens | 1.5 | Avanto | 2005 | VB17A | 60 | 40/170 |
University Hospital Southampton UK | Siemens | 1.5 | Avanto | 2006 | VB17A | 60 | 40/200 |
Barts Heart Center London UK | Siemens | 1.5 | Aera | 2014 | VD13A | 70 | 45/200 |
Barts Heart Center London UK | Siemens | 1.5 | Aera | 2015 | VE11A | 70 | 45/200 |
The Heart Hospital London UK | Siemens | 1.5 | Avanto | 2009 | VD13A | 70 | 40/200 |
Charité Campus Buch Germany | Siemens | 1.5 | Avanto | 2007 | VB13B | 60 | 40/200 |
University of Virginia US | Siemens | 1.5 | Avanto | 2005 | VB17A | 60 | 45/200 |
University of Virginia US | Siemens | 1.5 | Avanto | 2015 | VD13A | 60 | 45/200 |
SIEMENS EU | Siemens | 1.5 | Aera | 2009 | VE11 | 70 | 45/200 |
UZ Leuven Belgium | Philips | 1.5 | Ingenia | 2007 | R5.1.7 | 60 | 45/ 200 |
UZ Leuven Belgium | Philips | 1.5 | Achieva XR | 2014 | R5.1.7 | 70 | 33/122 |
Beth Israel Deaconess Medical Center, US | Philips | 1.5 | Achieva | 2005 | R3.2 | 60 | 33/180 |
NIH Bethesda US | Siemens | 1.5 | Aera | 2012 | VD13A | 70 | 45/200 |
St Thomas’ Hospital UK | Philips | 3 | Achieva TX | 2007 | R3.2.3 | 60 | 40/200 |
St Thomas’ Hospital UK | Siemens | 3 | Biograph mMR | 2013 | VB20P | 60 | 45/200 |
Fondazione Toscana Monasterio Pisa Italy | Philips | 3 | Ingenia | 2012 | R5.1.8 | 70 | 45/200 |
Oslo University Hospital Norway | Philips | 3 | Ingenia | 2011 | 5.1.7 | 70 | 45/200 |
Oslo University Hospital Norway | Siemens | 3 | Skyra | 2014 | VE11 | 70 | 45/120 |
CRIC Bristol UK | Siemens | 3 | Skyra | 2009 | VD13C | 60 | 44/180 |
Diagnostikum Berlin Germany | Siemens | 3 | Skyra | 2012 | VE11 | 70 | 45/200 |
University of Aberdeen Scotland UK | Philips | 3 | Achieva TX | 2015 | R5.1.7 | 60 | 80/100 |
NIH Bethesda US | Siemens | 3 | Verio | 2009 | VB17 | 70 | 33/125 |
Leiden UMC The Netherlands | Philips | 3 | Achieva TX | 2012 | R5.1.8.2 | 70 | 45/200 |
MUMC The Netherlands | Philips | 3 | Achieva TX | 2011 | R 3.2 | 60 | 40/200 |
Wythenshawe Manchester UK | Siemens | 3 | Skyra | 2014 | VE11 | 70 | 45/200 |
Copenhagen University Hospital Denmark | Siemens | 3 | Verio | 2010 | VB17 | 70 | 45/200 |
Charles Perkins Sydney Australia | GE | 3 | Discovery MR750w | 2014 | DV25 | 70 | 44/200 |
BHF Glasgow Center UK | Siemens | 3 | Prisma | 2015 | VE11 | 60 | 80/200 |
INSERM U1044 France | Siemens | 3 | Prisma | 2015 | VE11 | 60 | 80/200 |
DHZ Berlin Germany | Philips | 3 | Ingenia | 2011 | R5.1.8 | 70 | 45/200 |
St George’s University London UK | Philips | 3 | Achieva TX | 2012 | R5.1 | 60 | 40/150 |
RBHT London UK | Siemens | 3 | Skyra PTX | 2011 | VD13C | 70 | 43/180 |
Barts Heart Center London UK | Siemens | 3 | Prisma | 2015 | VE11 | 60 | 80/200 |
Leeds General Infirmary UK | Philips | 3 | Achieva TX | 2010 | R5.2 | 60 | 40/120 |
Montreal Heart Institute Canada | Siemens | 3 | Skyra | 2012 | VD13A | 70 | 45/200 |
PTB Germany | Siemens | 3 | Verio | 2010 | VB17A | 70 | 45/200 |
University of Virginia US | Siemens | 3 | Skyra | 2011 | VE11A | 70 | 45/200 |
UZ Leuven Belgium | Philips | 3 | Ingenia | 2010 | R5.1.7 | 70 | 45/200 |
NIH Bethesda US | Siemens | 3 | Skyra | 2012 | VD13A | 70 | 45/200 |
University of Queensland Australia | Siemens | 7 | Magnetom 7 | 2013 | VB17B | 60 | 72/200 |
University of Queensland Australia | Siemens | 3 | Trio TIM | 2008 | VB17A | 60 | 45/200 |
Glenfield Hospital Leicester UK | Siemens | 3 | Skyra | 2010 | VD13A | 70 | 45/200 |
Baker IDI Australia | Siemens | 3 | Prisma | 2014 | VD13D | 60 | 80/200 |
NIST USd
| Agilent | 1.5 | Varian | 2013 | VnmrJ 4 | 14 | 300/475 |
NIST USd
| Agilent | 1.5 | Varian | 2013 | VnmrJ 4 | 14 | 300/475 |