Multi-Center Multi-Vendor Validation of Liver QSM in Patients with Iron Overload

Author

Lu Mao

Subject characteristics

Descriptive statistics for subject-level variables are tabulated below by site and overall. Quantitative variables are summarized by median (inter-quartile range; IQR) and categorical variables by N (%).

Table 1. Patient-level summary.
UW (N = 51) UTSW (N = 41) JHU (N = 27) Stanford (N = 38) Overall (N = 157)
Age 50 (21.5, 59) 46 (36, 56) 41 (18.5, 58.5) 17 (12.2, 21.8) 39 (19, 55)
Sex - m 33 (64.7%) 24 (58.5%) 14 (51.9%) 20 (52.6%) 91 (58%)
Sex - f 18 (35.3%) 17 (41.5%) 13 (48.1%) 18 (47.4%) 66 (42%)
Weight 75.3 (65.3, 97.3) 83.6 (61.4, 103) 66.2 (58.5, 80.5) 52 (33, 67) 69 (57.8, 90.1)
Height 172.7 (162.6, 178) 172.7 (162.3, 182.9) 165.1 (158.8, 172.5) 154 (139.6, 165) 167.6 (157.8, 177.8)
Ferriscan 3.4 (2, 6.6) 1.3 (0.7, 2.5) 3 (1.1, 6.8) 3 (1.5, 8) 2.6 (1.2, 6.5)

Linear regressions of QSM vs R2* and QSM vs LIC

Numbers of observations per site, field strength (FS), and test/retest are tabulated below.

Table 2. Number (n) of observations per site, FS, and test/retest
Site FS Retest n
UW 1.5 test 24
UW 1.5 retest 24
UW 3.0 test 27
UW 3.0 retest 30
UTSW 1.5 test 35
UTSW 1.5 retest 35
UTSW 3.0 test 31
UTSW 3.0 retest 30
JHU 1.5 test 14
JHU 1.5 retest 14
JHU 3.0 test 12
JHU 3.0 retest 14
Stanford 1.5 test 33
Stanford 3.0 test 27

QSM vs R2*

Site-specific regression lines of QSM vs R2* for each FS and test/retest scenario are plotted below. It appears that test data show stronger associations than retest data do.

We perform F-tests (with 2 degrees of freedom for intercept and slope) to compare the regression lines between pairs of sites. The p-values are summarized in Table 3a.

Table 3a. P-values for pairwise tests of site-specific regression lines for QSM vs R2*
UW vs UTSW UW vs JHU UW vs Stanford UTSW vs JHU UTSW vs Stanford JHU vs Stanford
1.5T 0.355 <0.001 0.015 0.002 0.014 <0.001
3.0T 0.41 <0.001 0.157 <0.001 0.295 <0.001

QSM vs LIC

Site-specific regression lines of QSM vs liver iron concentration (LIC) for each FS and test/retest scenario are plotted below. Test data also show stronger associations than retest data do.

Similarly, we perform F-tests to compare the regression lines between pairs of sites. The p-values are summarized in Table 3b.

Table 3b. P-values for pairwise tests of site-specific regression lines for QSM vs LIC
UW vs UTSW UW vs JHU UW vs Stanford UTSW vs JHU UTSW vs Stanford JHU vs Stanford
1.5T 0.182 <0.001 0.09 0.003 0.004 <0.001
3.0T <0.001 0.089 <0.001 0.003 0.003 0.013

Repeatability & reproducibility of QSM

Test-retest repeatability

Bland-Altman plots (difference vs mean) for test-retest QSM are plotted by FS and overall below. Data points are color-coded by site.

Why so few data points for 3T? Many subjects do not have full pairs of test-retest data:

# A tibble: 137 × 7
    UID   Site     FS        test    retest     mean     diff
    <chr> <fct>    <chr>    <dbl>     <dbl>    <dbl>    <dbl>
  1 J007  JHU      3T     1.16    NA        NA       NA      
  2 J013  JHU      3T    -0.124   NA        NA       NA      
  3 J016  JHU      3T     0.946   NA        NA       NA      
  4 J017  JHU      3T    -0.370   NA        NA       NA      
  5 J020  JHU      3T     1.07    NA        NA       NA      
  6 J021  JHU      3T    -0.101   NA        NA       NA      
  7 J026  JHU      3T     0.536    0.524     0.530   -0.0127 
  8 J029  JHU      3T     0.690    0.822     0.756    0.132  
  9 J031  JHU      3T    -0.339   -0.138    -0.238    0.201  
 10 J034  JHU      3T     0.0373   0.0251    0.0312  -0.0121 
 11 J035  JHU      3T    -0.0526  -0.0501   -0.0513   0.00244
 12 J036  JHU      3T     1.39     1.94      1.66     0.547  
 13 J039  JHU      3T    NA       -0.278    NA       NA      
 14 J040  JHU      3T    NA        3.16     NA       NA      
 15 J041  JHU      3T    NA        0.0605   NA       NA      
 16 J042  JHU      3T    NA       -0.140    NA       NA      
 17 J043  JHU      3T    NA       -0.356    NA       NA      
 18 J045  JHU      3T    NA       -0.344    NA       NA      
 19 J054  JHU      3T    NA       -0.00491  NA       NA      
 20 J055  JHU      3T    NA        1.20     NA       NA      
 21 S004  Stanford 3T    -0.320   NA        NA       NA      
 22 S005  Stanford 3T    -0.174   NA        NA       NA      
 23 S007  Stanford 3T    -0.403   NA        NA       NA      
 24 S008  Stanford 3T     0.829   NA        NA       NA      
 25 S010  Stanford 3T     1.40    NA        NA       NA      
 26 S011  Stanford 3T    -0.131   NA        NA       NA      
 27 S012  Stanford 3T     0.206   NA        NA       NA      
 28 S013  Stanford 3T    -0.207   NA        NA       NA      
 29 S015  Stanford 3T     1.39    NA        NA       NA      
 30 S017  Stanford 3T     0.137   NA        NA       NA      
 31 S018  Stanford 3T    -0.313   NA        NA       NA      
 32 S019  Stanford 3T    -0.276   NA        NA       NA      
 33 S020  Stanford 3T     0.448   NA        NA       NA      
 34 S022  Stanford 3T     0.450   NA        NA       NA      
 35 S023  Stanford 3T     0.715   NA        NA       NA      
 36 S024  Stanford 3T     0.0279  NA        NA       NA      
 37 S026  Stanford 3T     1.68    NA        NA       NA      
 38 S027  Stanford 3T     1.42    NA        NA       NA      
 39 S028  Stanford 3T     0.956   NA        NA       NA      
 40 S029  Stanford 3T     0.329   NA        NA       NA      
 41 S030  Stanford 3T     2.12    NA        NA       NA      
 42 S031  Stanford 3T    -0.364   NA        NA       NA      
 43 S032  Stanford 3T    -0.404   NA        NA       NA      
 44 S033  Stanford 3T    -0.263   NA        NA       NA      
 45 S035  Stanford 3T    -0.371   NA        NA       NA      
 46 S036  Stanford 3T     0.716   NA        NA       NA      
 47 S037  Stanford 3T    -0.142   NA        NA       NA      
 48 T001  UTSW     3T     0.239   NA        NA       NA      
 49 T002  UTSW     3T    -0.263   NA        NA       NA      
 50 T005  UTSW     3T    -0.304   NA        NA       NA      
 51 T006  UTSW     3T     0.0606  NA        NA       NA      
 52 T007  UTSW     3T     0.240   NA        NA       NA      
 53 T008  UTSW     3T    -0.158   NA        NA       NA      
 54 T009  UTSW     3T    -0.207   NA        NA       NA      
 55 T010  UTSW     3T    -0.469   NA        NA       NA      
 56 T012  UTSW     3T     0.450   NA        NA       NA      
 57 T013  UTSW     3T    -0.429   -0.375    -0.402    0.0548 
 58 T014  UTSW     3T    -0.298   NA        NA       NA      
 59 T015  UTSW     3T    -0.185   NA        NA       NA      
 60 T016  UTSW     3T     1.71     1.63      1.67    -0.0793 
 61 T017  UTSW     3T    -0.147   -0.127    -0.137    0.0200 
 62 T019  UTSW     3T    -0.418   -0.422    -0.420   -0.00383
 63 T020  UTSW     3T    -0.351   -0.173    -0.262    0.178  
 64 T021  UTSW     3T    -0.260   -0.292    -0.276   -0.0319 
 65 T023  UTSW     3T    -0.296   -0.201    -0.249    0.0953 
 66 T024  UTSW     3T     0.230    0.236     0.233    0.00636
 67 T025  UTSW     3T    -0.209   -0.200    -0.205    0.00898
 68 T026  UTSW     3T    -0.202   -0.221    -0.212   -0.0188 
 69 T027  UTSW     3T     0.137   -0.0791    0.0287  -0.216  
 70 T028  UTSW     3T    -0.0669  -0.0939   -0.0804  -0.0270 
 71 T029  UTSW     3T    -0.341   -0.370    -0.356   -0.0282 
 72 T030  UTSW     3T    -0.115   -0.104    -0.109    0.0103 
 73 T031  UTSW     3T    -0.173   -0.143    -0.158    0.0298 
 74 T032  UTSW     3T    -0.0813  -0.0872   -0.0843  -0.00591
 75 T033  UTSW     3T    -0.148   -0.158    -0.153   -0.00940
 76 T034  UTSW     3T    -0.201   -0.190    -0.196    0.0106 
 77 T035  UTSW     3T     0.00189 -0.0365   -0.0173  -0.0384 
 78 T036  UTSW     3T    -0.0922  -0.106    -0.0990  -0.0135 
 79 T038  UTSW     3T    NA        0.0763   NA       NA      
 80 T039  UTSW     3T    NA       -0.419    NA       NA      
 81 T040  UTSW     3T    NA       -0.321    NA       NA      
 82 T041  UTSW     3T    NA       -0.146    NA       NA      
 83 T042  UTSW     3T    NA        1.21     NA       NA      
 84 T043  UTSW     3T    NA        1.36     NA       NA      
 85 T045  UTSW     3T    NA       -0.185    NA       NA      
 86 T046  UTSW     3T    NA       -0.101    NA       NA      
 87 T048  UTSW     3T    NA       -0.219    NA       NA      
 88 T049  UTSW     3T    NA        0.0357   NA       NA      
 89 W001  UW       3T     0.350   NA        NA       NA      
 90 W003  UW       3T     0.118   NA        NA       NA      
 91 W004  UW       3T    -0.213   NA        NA       NA      
 92 W005  UW       3T     0.462   NA        NA       NA      
 93 W007  UW       3T    -0.252   NA        NA       NA      
 94 W009  UW       3T    -0.374   NA        NA       NA      
 95 W010  UW       3T    -0.0729  NA        NA       NA      
 96 W011  UW       3T     1.06    NA        NA       NA      
 97 W012  UW       3T    -0.277   NA        NA       NA      
 98 W013  UW       3T     0.233   NA        NA       NA      
 99 W014  UW       3T     0.675   NA        NA       NA      
100 W015  UW       3T    -0.329   NA        NA       NA      
101 W016  UW       3T     0.337   NA        NA       NA      
102 W018  UW       3T    -0.170   NA        NA       NA      
103 W019  UW       3T     1.31    NA        NA       NA      
104 W021  UW       3T     0.753   NA        NA       NA      
105 W023  UW       3T     0.703   NA        NA       NA      
106 W024  UW       3T     1.09    NA        NA       NA      
107 W025  UW       3T     0.495    0.339     0.417   -0.156  
108 W026  UW       3T     0.362    0.317     0.340   -0.0452 
109 W027  UW       3T    -0.291   -0.257    -0.274    0.0337 
110 W029  UW       3T     0.0145   0.281     0.148    0.266  
111 W030  UW       3T    -0.107   -0.0512   -0.0793   0.0563 
112 W032  UW       3T     0.0155  -0.000904  0.00732 -0.0165 
113 W033  UW       3T    -0.148    0.165     0.00832  0.313  
114 W034  UW       3T    -0.107   -0.202    -0.154   -0.0946 
115 W035  UW       3T     0.619   NA        NA       NA      
116 W038  UW       3T    NA        0.671    NA       NA      
117 W039  UW       3T    NA       -0.474    NA       NA      
118 W040  UW       3T    NA        0.729    NA       NA      
119 W041  UW       3T    NA        0.957    NA       NA      
120 W042  UW       3T    NA       -0.00725  NA       NA      
121 W043  UW       3T    NA        0.0606   NA       NA      
122 W044  UW       3T    NA       -0.0710   NA       NA      
123 W045  UW       3T    NA       -0.187    NA       NA      
124 W046  UW       3T    NA       -0.246    NA       NA      
125 W047  UW       3T    NA       -0.0294   NA       NA      
126 W048  UW       3T    NA       -0.184    NA       NA      
127 W049  UW       3T    NA        0.178    NA       NA      
128 W050  UW       3T    NA        0.491    NA       NA      
129 W051  UW       3T    NA        0.185    NA       NA      
130 W052  UW       3T    NA       -0.0851   NA       NA      
131 W053  UW       3T    NA       -0.208    NA       NA      
132 W054  UW       3T    NA       -0.170    NA       NA      
133 W055  UW       3T    NA        0.271    NA       NA      
134 W056  UW       3T    NA       -0.0747   NA       NA      
135 W057  UW       3T    NA        0.692    NA       NA      
136 W058  UW       3T    NA        0.318    NA       NA      
137 W059  UW       3T    NA        0.194    NA       NA      

The bias (mean test-retest difference), repeatability coefficient (RC; range covering 95% test-retest differences), intraclass correlation coefficient (ICC) with 95% confidence interval (CI) and p-value (for testing ICC = 0) are presented in Table 4 below.

Table 4. Test-retest repeatability analysis of QSM.
FS Bias RC ICC P
1.5T -0.076 1.024 0.693 (0.552, 0.795) <0.001
3T 0.034 0.271 0.959 (0.92, 0.979) <0.001
Overall -0.041 0.863 0.746 (0.648, 0.819) <0.001

Field strength reproducibility

The Bland-Altman plot for reproducibility between 1.5T and 3T is shown below, with bias, ICC (95% CI), and p-value indicated on the figure.

Sex differences in LIC

LIC values are compared between females and males by site and overall in Table 5 below. The p-values are based on the Wilcoxon rank sum test.

Table 5. Median (IQR) of LIC by site and sex.
Site Female Male P
UW 3.6 (2.2, 6.3) 3.4 (1.8, 7.5) 0.805
UTSW 2.4 (1.4, 5.8) 0.9 (0.7, 1.6) 0.019
JHU 3.8 (1.2, 7.6) 2.7 (1.1, 3.7) 0.409
Stanford 6.7 (2.4, 9.9) 2.5 (1.2, 3.9) 0.023
Overall 3.8 (1.8, 7.5) 2.1 (1, 4) 0.009

The following boxplot visualizes the comparisons.

Sex differences in QSM vs (R2*, LIC)

Sex-specific regression lines of QSM vs R2* for each FS and test/retest scenario are plotted below, with F-test p-values comparing the two lines indicated on the plots.

Similarly, sex-specific regression lines of QSM vs LIC for each FS and test/retest scenario are plotted below, with F-test p-values comparing the two lines indicated on the plots.