European Journal of Radiology 165 (2023) 110942

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European Journal of Radiology

journal homepage: www.elsevier.com/locate/ejrad

Quantification of cross-vendor variation in ADC measurements in

vendor-specific prostate MRI-protocols
Jakob M Møller a, *, Lars Boesen b, Adam Espe Hansen c, Karen Kettles d, Vibeke Løgager e
a
Dep. of Radiology, Copenhagen University Hospital, Herlev-Gentofte, Denmark, Borgmester Ib Juuls vej 17, DK-2730 Herlev, Denmark
b
Dep. of Urology, Copenhagen University Hospital, Herlev-Gentofte, Denmark
c
Dep of radiology, Copenhagen University Hospital, Rigshospitalet and dep. of clinical medicine Copenhagen University, Copenhagen, Denmark
d
Siemens Healthineers, Ballerup, Denmark
e
Dep. of Radiology, Copenhagen University Hospital, Herlev-Gentofte, Denmark

A R T I C L E I N F O A B S T R A C T

Keywords: Purpose: The purpose of this study was to quantify the variability of Apparent Diffusion Coefficient (ADC) and test
MRI if there were statistically significant differences in ADC between MRI systems and sequences.
ADC Method: With a two-chamber cylindrical ADC phantom with fixed ADC values (1,000 and 1,600x10− 6 mm2/s) a
Prostate cancer
single-shot (ss) Echo Planar Imaging (EPI), a multi-shot EPI, a reduced field of view DWI (zoom) and a Turbo Spin
Phantom study
Echo DWI sequence were tested in six MRI systems from three vendors at 1.5 T and 3 T. Technical parameters
PI-RADS
were according to Prostate Imaging Reporting and Data System Version 2.1. ADC maps were calculated by
vendor specific algorithms. Absolute and relative differences in ADC from the phantom-ADC were calculated and
differences between sequences were tested.
Results: At 3 T absolute differences from phantom given ADC (~1,000 and ~ 1,600x10− 6 mm2/s) were − 83 –
42x10− 6 mm2/s (-8.3%-4.2%) and − 48 – 15x10− 6 mm2/s (-3%-0.9%), respectively and at 1.5 T absolute dif­
ferences were − 81 – 26x10− 6 mm2/s (-2.6%-8.1%) and − 74 – 67x10− 6 mm2/s (-4.6%-4.2%), respectively.
Significant statistical differences in ADC measurements were identified between vendors in all sequences except
for ssEPI and zoom at 3 T in the 1,600x10− 6 mm2/s phantom chamber. Significant differences were also iden­
tified between ADC measurements at 1.5 T and 3 T in some of the sequences and vendors, but not all.
Conclusion: The variation of ADC between different MRI systems and prostate specific DWI sequences is limited in
this phantom study and without apparent clinical relevance. However, prospective multicenter studies of
prostate cancer patients are needed for further investigation.

1. Introduction
Diffusion weighted MRI (DWI) is an essential element in the detec­
tion of clinically significant (cs) prostate cancer (PCa) especially in the
peripheral zone were 70% of PCa is located [1]. MRI guided detection of
csPCa can be performed using the Prostate Imaging Reporting & Data
System (PI-RADS) version 2.1 [2] where a low-intensity area on the
Apparent Diffusion Coefficient (ADC) map corresponding to a high-
signal intensity area on DWI sequence is suspicious for csPCa.
There is a strong association between the aggressiveness of prostate
cancer and the Gleason score [3], with a significant correlation of
Gleason score with ADC that has been advocated as an image-based
biomarker of tumor aggressiveness [4–9]. Moreover, ADC has been
studied and found useful as a biomarker of treatment response after focal
therapy in prostate cancer [10–14].
The standard DWI sequence is performed as a single shot (ss) Echo
Planar Imaging (EPI), acquired rapidly thereby lowering the risk of
motion artifacts, while maintaining a high signal-to-noise ratio (SNR).
Unfortunately, ssEPI is very prone to susceptibility artifacts, commonly
caused by rectal gas and metal prostheses [15]. To reduce susceptibility
artifacts, correct patient preparation and new DWI sequences have been
established. Multi-shot (ms) EPI reduces blurring but can increase

Abbreviations: ADC, Apparent Diffusion Coefficient; ADCcorr, temperature corrected Apparent Diffusion Coefficient; cs, clinical significant; DWI, Diffusion
Weighted Imaging; EPI, Echo Planar Imaging; ms, multi-shot; PCa, Prostate Cancer; PI-RADS, Prostate Imaging Reporting & Data System; PVP, polyvinylpyrrolidone;
ROI, Region of Interest; SNR, Signal to Noise Ratio; Ss, single-shot; TSE, Turbo Spin Echo.
* Corresponding author.
E-mail address: jakob.moeller@regionh.dk (J.M. Møller).

https://doi.org/10.1016/j.ejrad.2023.110942
Received 9 March 2023; Received in revised form 14 June 2023; Accepted 19 June 2023
Available online 21 June 2023
0720-048X/© 2023 Elsevier B.V. All rights reserved.
J.M. Møller et al. European Journal of Radiology 165 (2023) 110942

sensitivity to motion, reduced field of view acquisitions (zoom) decrease
anatomic distortion and susceptibility artifacts, and lastly ss Turbo Spin
Echo (TSE) is less sensitive to susceptibility and motion effects but SNR
is lower [16].
The ADC derived from DWI is calculated as the slope of the signal-
intensity curve from the DWI vs b-value plot (the “b” value depends
on the strength and timing of the magnetic field gradients employed to
generate diffusion weighting). Utilization of the ADC as a biomarker
across different imaging centers can be challenged by the aid of different
MRI systems, DWI sequences and algorithms to calculate ADC.
Recently, the variation of ADC in a phantom study of a standardized
ssEPI sequence has been published [17]. In a multi-center study of one 3
T system and six 1.5 T systems, the ADC variation between the systems
was 4% when vendor specific ADC maps were used. However, the dif­
ferences between systems were not tested [17]. Analysis was performed
offline not using the vendor specific modelling process and not in the
clinical daily used systems.
As focus was to mimic clinical workflow, manufacturer-provided
DWI sequences and software for ADC calculation were used. The
purpose of this study was to quantify the variability and test the sig­
nificance of ADC measurements differences performed in four relevant
DWI sequences performed on three vendor 1.5 T and 3 T systems.
2. Material and methods
Data were acquired in two different radiology departments in the
Capital region of Denmark (Herlev-Gentofte Hospital and Rig­
shospitalet, Copenhagen University hospitals) where four different DWI
sequences were tested in 6 different MRI systems.
2.1. Phantom
A cylindrical phantom with a diameter of 15 cm with two chambers
filled with an aqueous polyvinylpyrrolidone (PVP) solution and a build-
in thermometer was used (HQ Imaging Germany). The desired ADC was
adjusted by the PVP concentration (1,000 × 10− 6 mm2/s and 1,600 ×
10− 6 mm2/s at 20 ◦ C).

Table 1
MRI parameters for the diffusion weighted sequences.
ssEPI Artist 1.5 T GE Ambition 1.5 T Sola 1.5 T Siemens Premiere 3 T GE MR 7700 3 T Vida 3 T Siemens
Healthcare Philips Healthineers Healthcare Philips Healthineers

FOV (mm) 200x200 200x200 200x200 200x200 200x200 200x200

TR (ms) 5898 3226 4100 3500 3500 4000
TE (ms) 70,6 72 54 53.9 57 57
b (s/mm2) 50,800 50,800 50,800 50,800 50,800 50,800
Dwi directions 4 4 4 4 4 4
Acc. factor 1 2 2 1 3 2
Resolution 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5
(mm)
BW (Hz/pixel) 1953 2224 1388 1953 2479 1524
Averages pr b 2;10 1;10 2;10 2;10 2;10 2;10
Time (min:sec) 3:38 3:36 3:39 2:10 2:10 3:26
msEPI NA NA
FOV (mm) 200x200 200x200 200x200 200x200
TR (ms) 4690 4630 2997 4200
TE (ms) 69,1 49 54 46
b (s/mm2) 50,800 50,800 50,800 50,800
Dwi directions 4 4 4 4
Acc. factor 1 2 1 2
Resolution 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5
(mm)
BW (Hz/pixel) 1953 1157 1993 1078
Averages pr b 2;8 1;2 3;10 1;2
Time (min:sec) 4:51 4:53 4:00 4:26
Zoom
FOV (mm) 200x100 200x67 200x100 200x100 200x100 200x100
TR (ms) 4709 2988 4000 4500 5363 4000
TE (ms) 66.5 70 57 48.7 44 59
b (s/mm2) 50,800 50,800 50,800 50,800 50,800 50,800
Dwi directions 4 4 4 4 4 4
Acc. factor 1 2 (sense) 1 1 1 –
Resolution 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5 3x2.5x2.5
(mm)
BW (Hz/pixel) 1953 2392 1226 1953 2927 1136
Averages pr b 3;10 1;3 2;10 3;12 1;8 2;11
Time (min:sec) 3:08 2:29 3:30 3:27 5:00 3:38
TSE NA NA NA NA
FOV (mm) 200x200 200x200
TR (ms) 2949 3000
TE (ms) 66 47
b (s/mm2) 50,800 50,800
Dwi directions 4 4
Acc. factor 1 3
Resolution 3x2.5x2.5 3x2.5x2.5
(mm)
BW 965 872
Averages pr b 4;8 2;8
Time (min:sec) 3:32 4:30

ADC, apparent diffusion coefficient; ssEPI, single-shot Echo Planar Imaging; zoom, reduced field of view diffusion weighted sequence; msEPI, multi-shot Echo Planar
Imaging; TSE, Turbo Spin Echo diffusion weighted sequence; FOV, field of view; TR, time to repeat; TE, time to echo; Acc, acceleration; BW, receiver bandwidth.

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J.M. Møller et al.
2.2. MR systems
The phantom studies were performed in three 3 T systems: Premiere
(GE healthcare, Milwaukee, WI), 80 mT/m gradient amplitude and 200
T/m/s slew-rate, MR 7700 (Philips, Best, the Netherlands), 65 mT/m
gradient amplitude and 220 T/m/s slew-rate, and Magnetom Vida
(Siemens Healthineers, Erlangen, Germany), 60mT/m gradient ampli­
tude and 200 T/m/s slew-rate. A similar approach was used for three
1.5 T systems: Artist (GE healthcare, Milwaukee, WI), 44 mT/m gradient
amplitude and 200 T/m/s slew-rate, Ambition (Philips, Best, the
Netherlands), 45 mT/m gradient amplitude and 200 T/m/s slew-rate,
and Magnetom Sola (Siemens Healthineers, Erlangen, Germany),
45mT/m gradient amplitude and 200 T/m/s slew-rate.
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European Journal of Radiology 165 (2023) 110942
2.3. MRI protocols
From the vendor supplied default library, four specific DWI se­
quences were selected compliant to the technical specifications of the PI-
RADS version 2.1 guidelines [2]; if not applicable, a sequence was
constructed according to them. Selected sequences were ssEPI, msEPI,
zoom and TSE DWI, although not all sequences were provided by all
vendors due to vendor technology or licenses on each system. Avail­
ability and specific parameters are presented in Table 1. Each sequence
was acquired 5 times within one hour, with temperature measurement
at each time point.
2.4. Post-processing
ADC maps were calculated using vendor-specific software (AW
Server version 3.2, GE Healthcare, Milwaukee, WI; Intellispace version
Fig. 1. Scatterplot of all corrected ADC measure­
ments for the ADC = 1,000 × 10− 6 mm2/s (top) and
ADC = 1,600x 10− 6 mm2/s (bottom) chambers of the
phantom. ADCcorr, temperature corrected apparent
diffusion coefficient; ssEPI, single-shot Echo Planar
Imaging; zoom, reduced field of view diffusion
weighted sequence; msEPI, multi-shot Echo Planar
Imaging; TSE, Turbo Spin Echo diffusion weighted
sequence; Artist, 1.5 T GE Healthcare; Ambition, 1.5 T
Philips; Sola, 1.5 T Siemens Healthineers; Premier, 3
T GE Healthcare; MR 7700; 3 T Philips; Vida, 3 T
Siemens Healthineers.
J.M. Møller et al.
11, Philips, Best, the Netherlands; Syngo.via version XB60A, (Siemens
Healthineers, Erlangen, Germany).
A circular region of interest (ROI) of 130 mm in diameter (60 mm for
zoom DWI) was placed in the center of both chambers of the phantom to
measure mean of the ADC in each acquisition. All measurements were
corrected for temperature effects above 20 ◦ C. The temperature cor­
rected ADC (ADCcorr) was calculated based on equation (1):
ADC
ADCcorr = (1)
ec(T− 20)
where T is the measured temperature in the phantom [18], and c =
0.0287 for ADC ~ 1,000 × 10− 6 mm2/s and c = 0.0261 for ADC ~ 1,600
× 10− 6 mm2/s.
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European Journal of Radiology 165 (2023) 110942
2.5. Statistics
ADC measurements were checked for normal distribution using the
Shapiro-Wilk test. The Mann-Whitney U two-sided test was used to test
vendor specific ADC dependence of field strength and the Kruskal-Wallis
test was used to test across the vendor systems. Absolute and relative
differences in measured ADCcorr to the phantom given ADC was calcu­
lated. Limits of agreement (loa) were calculated as the mean difference
of the ADC between two sequences plus/minus 1.96 times the standard
deviation of the differences. In the analysis, a p < 0.05 was considered
statistically significant. Statistical analysis was performed using SPSS
28.0 (IBM, Armonk, NY).
3. Results
The Shapiro-Wilk test showed that the distribution of ADC ~ 1000
Fig. 2. Scatterplot of relative average differences
from known phantom ADC for the ADC = 1,000 ×
10− 6 mm2/s (top) and ADC = 1,600 × 10− 6 mm2/s
(bottom) chambers of the phantom. ADC, apparent
diffusion coefficient; ssEPI, single-shot Echo Planar
Imaging; zoom, reduced field of view diffusion
weighted sequence; msEPI, multi-shot Echo Planar
Imaging; TSE, Turbo Spin Echo diffusion weighted
sequence; Artist, 1.5 T GE Healthcare; Ambition, 1.5 T
Philips; Sola, 1.5 T Siemens Healthineers; Premier, 3
T GE Healthcare; MR 7700; 3 T Philips; Vida, 3 T
Siemens Healthineers.
J.M. Møller et al. European Journal of Radiology 165 (2023) 110942

departed from normality (p < 0.05) whereas ADC ~ 1600 did not (p> Table 2
0.05). Based on the non-normality of one of the variables, non- P values from Mann-Whitney U test between 1.5 T and 3 T from the same vendor.
parametric tests were used. Fig. 1 shows all corrected ADC measure­ GE Philips Siemens
ments from all scanner vendors, sequences and repeated acquisitions as Healthcare Healthineers
well as both phantom chambers. Data form Fig. 1 are listed in Table S1. ssEPI ADC ~ 1000x10− 6 mm2/ 0.008 0.008 0.008
Fig. 2 shows the corresponding relative average differences from the s
expected phantom values. ssEPI ADC ~ 1600x10− 6 mm2/ 0.056 0.056 0.008
At 3 T absolute differences from phantom given ADC (~1,000 and ~ s
msEPI ADC ~ 1000x10− 6 0.056 na 0.008
1,600 × 10− 6 mm2/s) were − 83 – 42 x10− 6 mm2/s (-8.3% − 4.2%) and mm2/s
− 48 – 15 x10− 6 mm2/s (-3% − 0.9%), respectively and at 1.5 T absolute msEPI ADC ~ 1600x10− 6 0.095 na 0.016
differences were − 81 – 26 x10− 6 mm2/s (-2.6% − 8.1%) and − 74 – 67 mm2/s
x10− 6 mm2/s (-4.6% − 4.2%), respectively. zoom ADC ~ 1000x10− 6 mm2/ 0.008 0.008 0.008
s
There were statistically significant differences in ADCcorr between
zoom ADC ~ 1600x10− 6 mm2/ 0.008 0.222 0.008
vendors for all the sequences both at 1,5T and 3 T, except for zoom at 3 T s
in the 1,600 × 10− 6 mm2/s phantom chamber (Table S3). There were TSE ADC ~ 1000x10− 6 mm2/s na 0.008 na
statistically significant differences between ADCcorr measured at 1.5 T TSE ADC ~ 1600x10− 6 mm2/s na 0.016 na
and 3 T in some of the sequences and vendors, but not all (Table 2). In
the ADC ~ 1000 container at 1.5 T the maximum deviation was between
reproducibility studies of ADC. This ensures a high degree of repro­
ssEPI of Artist and Ambition (loa: 72.6–179.8 x10− 6 mm2/s), at 3 T the
ducibility across different sites and MR systems [19]. As compared to
maximum deviation was between msEPI of Premiere and ssEPI of Vida
earlier studies, the variations of ssEPI ADC between MR systems were
(loa: 107.0–142.6 × 10− 6 mm2/s) and regardless of field strength be­
similarly small despite differences in sequence parameters [17]. The
tween ssEPI of Artist and Vida (loa: 137.8–188.2 × 10− 6 mm2/s).
differences between the other sequences tested in our study were also
Repeatability coefficients for all sequences are listed in Table S2 and
small, indicating a high reproducibility of DWI sequences used in
difference plots in Figure S1.
prostate MRI.
The maximum deviation of ADC ~ 1000 was between ssEPI of Artist
4. Discussion
and Vida. This demonstrates that deviations larger than 188.2 × 10− 6
mm2/sare unlikely to be due to different technical factors but, instead,
In this phantom study of prostate DWI sequences, the ADC mea­
should be the result of biological change.
surement precision was tested in six different MRI systems using four
In a clinical setting there are more causes of ADC variations. At
types of DWI sequences. Despite the data revealing statistically signifi­
present there is no consensus whether the size and placement of ROI
cant differences between MR systems, vendors and sequences, very
influence this part of the ADC interpretation or not. The lowest mean
small absolute differences in ADC were recognized which equate to
value, assumed to be the area with the highest restricted diffusion [23],
presumably no clinical relevance in data reporting. It should be noted
has been used by some and the largest tumor extent was selected for
that phantom scanning produces homogenous high signal intensity im­
analysis, while a ROI drawn in the center of the tumor excluding the
ages without motion or perfusion effects and the possibility to use large
tumor edges [4] has been used by others. In case of several focal lesions
region-of-interests represents the best precision of data analysis that can
the largest has been chosen as index tumor [24]. These different ROI
be obtained [19].
strategies together with the technical calculation of the ADC map e.g.
When ADC is used as a biomarker of tumor aggressiveness and to
color-depth and interpolation introduces more variance in ADC
differentiate between benign and malignant tissue, the phantom-ADC
measurements.
variation between MR systems and DWI sequences should be lower
As a limitation, the current study focused on readily available DWI
than reported variations from clinical studies. Similar, when ADC is used
sequences as provided by the vendors fulfilling the PI-RADS version 2.1
as a biomarker of treatment response, the variation of phantom-ADC
technical recommendations. No attempt to standardize the sequence
should be lower than the lowest reported variation from clinical
parameters was made. While this may explain the minor, yet consistent
studies. Several studies have investigated ADC values to differentiate
and significant ADC differences across vendors and field strengths, our
csPCa from in-significant PCa. Boesen et al reported ADC = 1,472 (1,293
approach reflects the clinical reality facing MRI departments. However,
– 1,651) × 10− 6 mm2/s for Gleason 7 (3 + 4) in the peripheral zone and
prospective multicenter studies are needed for further investigation.
1,150 (1,054 – 1,248) × 10− 6 mm2/s in the transition zone [4], Gibbons
et al reported ADC = 1,200 +/- 260 × 10− 6 mm2/s in the peripheral
5. Conclusions
zone [6] and Panda et al reported ADC = 570 +/- 130 × 10− 6 mm2/s in
the transition zone for PI-RADS 4 and 5 lesions [7]. These clinically
The variation of ADC between different MRI systems and prostate
relevant variations in ADC are bigger than the measured variations in
specific DWI sequences is very small in this phantom study and has
this study. We therefore estimate that the measured ADC variations in
presumably no clinical relevance.
the phantoms do not have clinical relevance. In longitudinal studies both
at baseline and at follow-up, the ADC variations were bigger than those
CRediT authorship contribution statement
measured in our study [11,13,20]. However, to find out if ADC differ­
ences have clinical impact prospective studies are needed.
Jakob M Møller: Methodology, Investigation, Formal analysis,
An explanation for greater ADC variations of PCa measured by
Conceptualization, Writing – original draft. Lars Boesen: Methodology,
different DWI sequences and vendor MRI systems may be attributed to
Investigation, Formal analysis, Conceptualization, Writing – review &
the inconsistent and variation of b-value selection. Both the European
editing. Adam Espe Hansen: Methodology, Investigation, Formal
Society of Urogenital Radiology and the PI-RADS recommendations of b-
analysis, Conceptualization, Writing – review & editing. Karen Kettles:
values [2,21] have not necessarily been used in the previous studies
Methodology, Investigation, Formal analysis, Conceptualization,
[4,6,7,20] and the calculation of the ADC is strongly dependent on the b-
Writing – review & editing. Vibeke Løgager: Methodology, Investiga­
value selection, which in turn affects ADC estimates [22].
tion, Formal analysis, Conceptualization, Writing – review & editing.
The use of a phantom to measure ADC variability across different
MRI systems is recommended by the Quantitative Imaging Biomarkers
Alliance, which emphasizes the need for repeatability and

5
J.M. Møller et al.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ejrad.2023.110942.
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