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This is a repository copy of

Imaging of Nuclear Magnetic Resonance spin-lattice relaxation

activation energy in cartilage

.

White Rose Research Online URL for this paper:

http://eprints.whiterose.ac.uk/132801/

Version: Supplemental Material

Article:

Foster, RJ orcid.org/0000-0002-5337-3615, Damion, RA, Ries, ME

orcid.org/0000-0002-8050-3200 et al. (4 more authors) (2018) Imaging of Nuclear

Magnetic Resonance spin-lattice relaxation activation energy in cartilage. Royal Society

Open Science, 5. 180221. ISSN 2054-5703

https://doi.org/10.1098/rsos.180221

eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse

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Imaging of Nuclear Magnetic Resonance spin-lattice relaxation activation energy in cartilage

R.J. Foster, R.A. Damion, M.E. Ries, S.W. Smye, D.G. McGonagle, D.A. Binks, A. Radjenovic

Supplementary Information

This supplementary information is associated with the publication of the same title in Royal Society: Open Science.

Sample Details

Note that only relevant medical history related to musculoskeletal diagnoses has been included

Sample Identifier Type Details Results Presented

1 G18_11 Human 86 year old female. Main manuscript

2 Bovine Bovine Approx 18month old cow. Harvested approximately within 72hours of slaughter.

Main manuscript

3 G05_11 Human 67year old female, Osteomyelitis Supplementary Information

4 G24_09 Human 65 year old female, Spinal degeneration. Supplementary Information

5 G29_10R Human 66 year old male. Supplementary Information

6 G48_11R Med Human 70 year old male Supplementary Information

7 G48_11R Lat Human 70 year old male Supplementary Information

Imaging Details

Sample Repetition times (ms) Temperatures (C)* Matrix Size Resolution (µ/pixel) 1 200, 500, 1000, 1500, 4000,

8000

9.1, 12.5, 15.8, 20.0, 25.0, 29.4, 34.5

434x256 100x100

2 Varied at different temperatures see below 128x256 70x117

3 200, 500, 1000, 1500, 2500, 4000, 8000

7.1, 12.6, 17.5, 21.5, 27.7, 34.3, 38.8

225x355 70x70

4 200, 500, 1000, 1500, 3000, 5000

10.5, 21.0, 26.9, 30.5, 38.0**

256x256 170x170

5 200, 500, 1000, 1500, 3000, 5000

7.8, 15.7, 22.0, 29.1, 36.9,

185x330 70x70

6 200, 500, 1000, 1500, 3000, 5000

7.7, 15.3, 20.9, 26.0 , 36.3

120x270 100x100

7 110, 200, 300, 500, 1000, 1500, 2000, 4000, 8000, 16000

9.1, 17.0, 24.2, 33.3, 37.8

171x342 70x70

*For all samples (except #4 see note below), the temperature was monitored by a thermocouple within the bore of the magnet, using a standard Bruker NMR configuration. The temperature was automatically monitored during the whole imaging sequence and the temperature of imaging was taking as the (arithmetically fitted) average during the imaging sequence. The error in all temperature measurements is less than ±0.1°C. When changing the temperature, samples were given a minimum of 1 hour to equilibrate at the new temperature before starting the imaging sequence.

**There was a problem with the monitoring thermocouple when imaging this sample. Temperatures were taken as the user observed temperature whilst the imaging sequence was running. The error in these temperature measurements therefore is approximately ±1°C.

Bovine Cartilage (sample 2) imaging details

Sample Temperature

(°C) TR (ms) Averages

Bovine

8.1 295, 458, 634, 824, 1033, 1263, 1519, 1808, 2139, 2528, 2999, 3595, 4407,

5692, 9000 4

14.9 100, 287, 487, 703, 937, 1193, 1475, 1790, 2144, 2551, 3029, 3608, 4340, 5340,

6924, 11040 1

22.3 213, 440, 684, 946, 1231, 1543, 1886, 2268, 2699, 3195, 3776, 4478, 5368,

6582, 8500, 13440 1

30.0 100, 370, 660, 970, 1310, 1680, 2090, 2550, 3060, 3650, 4350, 5190, 6250,

7700, 10000, 16000 2

38.1 622, 966, 1338, 1740, 2181, 2666, 3206, 3816, 4516, 5337, 6331, 7589, 9304,

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T1 fitting

[image:3.595.29.532.119.745.2]

A number of pixels were chosen at random throughout the cartilage to investigate whether a mono-exponential T1 fit was suitable. Mono-exponential fits were a good fit for all data, with an r2 of greater than 0.99 in all cases within the cartilage tissue.

Figure I shows T1 fits for the same pixel at each temperature imaged. Figure II shows a series of pixels chosen at random from within the cartilage body in sample #3 at 21C.

Figure I. T1 fits for the same pixel at different temperatures. Sample #4 (G24_09).

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000 8000 Si g n a l In te n si ty (a rb u n it s)

TR (s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

4199.1343

Adj. R-Square 0.99931

Value Standard Error

B

T1 1.31751 0.03049 y0 7438.38462 67.50094

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000 8000 Si g n a l In te n si ty (Arb U n it s)

TR (s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

4036.46069

Adj. R-Square 0.99932

Value Standard Error

B T1y0 7470.135821.73179 86.691220.0461

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

3045.63788

Adj. R-Square 0.99942

Value Standard Error

B

T1 2.0342 0.05549

y0 7206.06908 91.71562

Si g n a l In te n si ty (a rb u n it s)

TR (s)

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

6849.12341

Adj. R-Square 0.99863

Value Standard Error

B

T1 2.22324 0.10066

y0 7063.28029 155.12553

TR (s)

Si g n a l In te n si ty (a rb u n it s)

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 Si g n a l In te n si ty (a rb u n it s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

2830.38507

Adj. R-Square 0.99932

Value Standard Error

B

T1 2.50447 0.08652 y0 6709.98166 118.53875

TR (s)

10C 21C

26.9C 30.5C

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[image:4.595.30.535.31.611.2]

Figure II T1 fits for a series of pixels chosen at random from within the cartilage at different depths. Imaging at 26.9C. Sample #4 (G24_09).

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 Si g n a l In te n si ty (a rb it a ry u n it s)

TR (s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

2327.68962

Adj. R-Square 0.9991

Value Standard Error

B T1 1.73727 0.05343

y0 4920.67588 66.06949

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000 8000 Si g n a l In te n si ty (a rb it a ry u n it s)

TR (s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

1332.04997

Adj. R-Square 0.9998

Value Standard Error

B

T1 1.82849 0.02736

y0 7952.55563 53.06312

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

3045.63788

Adj. R-Square 0.99942

Value Standard Error

B T1y0 7206.069082.0342 91.715620.05549

Si g n a l In te n si ty (a rb u n it s)

TR (s)

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 6000 7000 Si g n a l In te n si ty (a rb it a ry U n it s)

TR (s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

905.89866

Adj. R-Square 0.99981

Value Standard Error

B T1y0 7069.794112.20151 55.649760.03588

0 1 2 3 4 5

0 1000 2000 3000 4000 5000 Si g n a l In te n si ty (a rb it a ry u n it s)

TR (s)

Model T1SatRec (User)

Equation y = y0*(1-exp(-x/T1))

Reduced Chi-Sqr

1623.25527

Adj. R-Square 0.99936

Value Standard Error

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T1 and EA profiles for samples #3-#7

Error bars in T1 are smaller than the size of data points. Samples #1 and #2 are presented in the main manuscript. For all samples, a slice in the imaging sequence close to the centre of cartilage has been used for EA analysis. For

samples #1 - #3 and #5 - #7, this was either slice 4 or 5, in the centre of the imaging package (the exact number depended on the total number of slices used, which varied due to the physical size of the sample). These were chosen so that the slice used for analysis was well away from any effects close to the edge of the sample. The slice number used for each sample is indicated below. For sample #4, only four slices were imaged, but due to the relative larger sample size, all slices were close to the centre of the cartilage. Therefore slice 1 was chosen for analysis in this sample.

Note that the dotted lines are estimated delineations between the PBS and cartilage, and in especially between the cartilage and subchondral bone. A description of how these were estimated is given in the figure caption for Figure 2 in the main manuscript.

Samples #2, #4, #5 and #7 show small changes in T1 with position within the PBS at the highest temperatures, and sample #3 shows a greater scatter in the data at these temperatures. This is due to the fact that the samples were immersed in PBS, but due to the relative size within the imaging tube in the NMR, the surface of the PBS generated artefacts visible in the PBS at higher temperatures. Although the region of interest was chosen carefully to avoid these artefacts, there may have been some segments in the PBS that were affected. In addition, it is possible that there are some edge effects or partial volume effects at the PBS/cartilage interface. Care was taken in the choice of imaging parameters to minimise these artefacts, but it was not possible to completely remove them because the parameters were determined in order to obtain the best T1 data throughout the cartilage tissue.

However, we note that the change in T1 with position at the higher temperatures is small compared to the change in T1 with temperature, meaning that the effect on EA is small. The Arrhenius fits gave a goodness of fit, r2 of greater than 0.8 in all the random datasets sampled for visual checking of the fits.

[image:5.595.51.554.402.619.2]

Sample #3 (G05_11)

Figure III T1 and EA profiles for slice #4 of sample #3 (G05_11)

-1000 0 1000 2000 3000

0 2 4 6 8 10 12 14

7.1oC

12.6oC

17.5oC

21.5oC

27.7oC

34.3oC

38.8oC

T1

(s)

Distance into cartilage (µm)

PBS Cartilage Subchondral bone

-1000 0 1000 2000 3000

0 5 10 15 20 25 30 35 40

EA

(kJ/

mo

l)

Distance into cartilage (µm)

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[image:6.595.38.540.49.261.2]

Sample #4 (G24_09)

Figure IV T1 and EA profiles for slice #1 of sample #4 (G24_09)

[image:6.595.53.553.310.511.2]

Sample #5 (G29_10R)

Figure V T1 and EA profiles for slice #4 of sample #5 (G29_10R)

Sample #6 (G48_11R Med)

Figure VI T1 and EA profiles for slice #4 of sample #6 (G48_11R Med)

-2000 -1000 0 1000 2000 3000 4000

0 1 2 3 4 5 6 7 8 9 10 11

10o

C

21o

C

27o

C

31o

C

38o

C

T1

(s)

Distance into cartilage (µm) G24_09 Slice 1

PBS Cartilage Subchondral bone

-2000 -1000 0 1000 2000 3000 4000 5

10 15 20 25 30 35

EA

(kJ/

mo

l)

Distance into cartilage (µm) PBS

G24_09 Slice 1

Cartilage Subchondral bone

-2000 -1000 0 1000 2000 3000 4000 5000 6000 7000

0 1 2 3 4 5 6 7 8

7.8oC

15.7oC

22.0oC

29.1oC

36.9oC

T1

(s)

Distance into cartilage (µm)

Subchondral bone Cartilage

PBS

-2000 -1000 0 1000 2000 3000 4000 5000 6000 7000 0

2 4 6 8 10 12 14 16 18 20

EA

(kJ/

mo

l)

Distance into cartilage (µm)

Subchondral bone Cartilage

PBS

-2000 -1000 0 1000 2000 3000 4000 5000

0 1 2 3 4 5 6 7 8

7.7oC

15.3oC

26.0oC

36.3oC

T1

(s)

Distance into cartilage (µm)

Cartilage Subchondral bone PBS

-2000 -1000 0 1000 2000 3000 4000 5000 0

5 10 15 20 25 30 35 40

EA

(kJ/

mo

l)

Distance into cartilage (µm)

Subchondral bone Cartilage

[image:6.595.53.550.569.772.2]
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Sample #6 (G48_11RMed) moved during imaging after the T1 imaging data was obtained at 20.9C (NB: this imaging dataset was the first collected). This dataset was therefore omitted when calculating EA profiles for this sample. The sample did not move further during the imaging session at other temperatures.

Sample #6 was fitted from DICOM images of the datasets.

[image:7.595.50.552.120.329.2]

Sample #7 (G48_11R Lat)

Figure VII T1 and EA profiles for slice #3 of sample #6 (G48_11R Lat)

Due to a user error, the datasets for T1 imaging at 9.1 and 17.0C for sample #7 (G48_11RLat) were obtained with the slice packages rotated through 180 in the axial direction. The x and y positions of the slices remained the same. Upon post-processing, theT1-fitted data for each slice in the datasets at 9.1 and 17.0C were mirrored to return them to the same orientation as the datasets obtained at the other temperatures. Note that because the slice packages were rotated by 180, the slice order is reversed for 9.1 and 17.0C datasets.

Sample #7 was fitted from DICOM images of the datasets.

Exponential pre-factor analysis

The Arrhenius plots shown in Figure 3 also allow the exponential pre-factor, A, from the Arrhenius model to be

determined from the fitted intercepts. Figure VIII shows an example dataset of how T1 at 20C, EA and A vary with depth through the cartilage for sample #1 (G18_11).

Figure VIII T1, EA and exponential pre-factor, A, as a function of depth for slice #4 of sample #1 (G18_11)

The pre-factor, A, can be related to a rotational correlation time and this is an extrapolation into the inertial limit of a completely free rotor model (Carper et al, J PhysChem, 100 (1996) p4724). It must be noted though that there is an entropic term within A that is usually not considered in an Arrhenius type analysis.

-1000 0 1000 2000 3000 4000 5000

0 1 2 3 4 5 6 7 8

7.8oC

15.7oC

22.0oC

29.1oC

36.9oC

T1

(s)

Distance into cartilage (µm)

Subchondral bone Cartilage

PBS

-1000 0 1000 2000 3000 4000 5000 0

5 10 15 20 25 30

EA

(kJ/

mo

l)

Distance into cartilage (µm)

PBS Cartilage Subchondral bone

-3000 -2000 -1000 0 1000 2000 3000 4000

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

T1 data (20oC)

EA data 'A' pre-factor

T1

(s)

Distance into Cartilage (m) G18_11 (Sample #1) - slice 4

0 2 4 6 8 10 12 14 16 18 20

EA

(kJ/

mo

l)

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5

A (x10

[image:7.595.171.432.516.711.2]
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Data and Code Accessibility

Data associated with this work are available from the Research Data Leeds repository under a CC-BY 4.0 license at https://doi.org/10.5518/270.

The data for samples #1-#5 is uploaded in raw binary format taken directly from the Bruker NMR (Paravision). The data for samples #6 and #7 is uploaded in DICOM format. These were converted from the raw binary data using Paravision 5.1 (Bruker NMR).

Data for the figures plotted both in the main manuscript and the supplementary information is also uploaded to the same location in a single Excel spreadsheet with tabs labelled for each figure.

The code used for data analysis in this study is available from the Research Data Leeds repository under a GNU LGPL 3.0 license at https://doi.org/10.5518/271.

Figure

Figure I shows T1 fits for the same pixel at each temperature imaged. Figure II shows a series of pixels chosen at random from within the cartilage body in sample #3 at 21C
Figure II T1 fits for a series of pixels chosen at random from within the cartilage at different depths
Figure III T1 and EA profiles for slice #4 of sample #3 (G05_11)
Figure IV T1 and EA profiles for slice #1 of sample #4 (G24_09)
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