Comparison of Muscle Image Acquisition & Analysis Techniques

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1 Comparison of Muscle Image Acquisition & Analysis Techniques Toronto General Research Institute Andy Kin On Wong PhD Assistant UHN Scientist Scanco User Meeting, September 20, :15 pm

2 Muscle & Bone Measures in vivo 200 um 195 um pqct 500 um 500 um 1.0T pmri Muscle density (MD) Muscle cross-sectional area (MCSA) Subcutaneous fat area vbmd, bone microstructural & mechanical properties Muscle area / volume Subcutaneous, inter & intramuscular fat volume Muscle proton density Bone microstructure, area

3 1. T1-Weighted Fast Spin Echo MRI TR/TE: 600/21 ms, NEX = 3, echoes = 2, flip angle=40 o, bandwidth=25 khz, 10 x 1.0 mm thick contiguous slices 195 µm in-plane resolution Issue: Muscle and bone cannot be separated by using fixed thresholds Subcutaneous fat INTERmuscular fat Fascia line Muscle Adult with diabetes Older Adult INTRAmuscular fat Younger Adult

4 Participants with a range of muscle adiposity can be observed Can be performed on the GE 1.0T pmri within 10 minutes Or on any clinical MRI scanner

5 Patterned Involvement of Muscle Dystrophy

6 MRI inter/intra-muscular fat (IMF) segmentation & quantification Watershed Algorithm Region-growing Algorithm IMF Area (IMF.A) IMF Volume (IMF.V) Watershed lines guide separation of different tissue regions Region-growing algorithm colours in tissues within signal range

7 Precision of Manually-Segmented IMF Measures Short-term test-retest pmri/pqct Variable All Participants N=51 No Fx and No Antiresorptives N=17 RMSCV RMSSD LSC RMSCV RMSSD LSC MRI IMF.A (mm 2 ) 10.6% % MRI IMF.V (mm 3 ) 6.1% % One-year test-retest N=33 N=14 MRI IMF.A (mm 2 ) 14.9% % MRI IMF.V (mm 3 ) 17.1% % IMF volume accounts for up to 54% of the variance in muscle density

8 Semi-Automated Segmentation of IMF Manual exclusion of bone and subcutaneous fat Seed point & thresholding Dichotomize Island Pruning Island Pruning Revised threshold applied & and looped until T R (iteration n) = T R (iteration n-1) New muscle (M i ) and IMF (F i ) seed values revised threshold (T R ) T R = 1 + M i F i F i M i

9 Final Segmented IMF

10 Manual IMF Area (mm 2 ) pqct-derived Muscle Density (mg/cm3) Precision of Semi-Automatically Segmented IMF Measures Study Comparison Variable N RMSCV RMSSD ICC Hamilton CaMos(N=43) Test-Retest MCSA mm Age: 74.6±8.9 y Test-Retest IMFA mm BMI: 25.60±4.61 kg/m 2 Test-Retest pimfa % y = 1.14x R² = Semi-Auto IMF Area (mm 2 ) y = -0.43x R² = 0.47 y = -0.81x R² = Percentage IMF Area (%) (Auto or Manual)

11 Automated Segmentation of IMF

12 Other MR Imaging Techniques Fat/Water-suppression pulses Chemical Shift Fat-Water Separation (IDEAL, 3 Point Dixon) Diffusion tensor imaging MR Spectroscopy

13 Challenges with MR Imaging 1. Signal inhomogeneity (full body scanners) 2. Amplified fat signal (T1 and T2 bias) 3. Imperfect suppression pulses 4. Spectral complexities of fat 5. Eddy currents (phase shift)

14 Partial volume artifact mm mm mm mm mm Figure 1. Comparison of intramuscular fat discernibility among images of varying resolutions.

15 Muscle Quantification on peripheral Quantitative Computed Tomography (pqct) -Measures muscle area, volume, density -Proxy for inter+intra-muscular fat pqct (Stratec XCT 2000) ISSUE: Muscle and fat must be separated from one another and from bone 500 µm Outer threshold 40 mg/cm 3 Inner threshold 40 mg/cm 3 Filter: F03F05F05 Contour Mode: 3 Peel Mode: 2

16 Failed muscle segmentations Manually re-segment around muscle fascia

17 Precision & Accuracy of pqct Muscle Outcomes Reliability Data RMSCV (% error) Variable & Method Young Older SCI Water-Shed MD (mg/cm 3 ) Threshold MD (mg/cm 3 ) Water-Shed MCSA (mm 2 ) Threshold MCSA (mm 2 ) SCI = Spinal Cord Injury Muscle density accounts for 54% of the variance in inter+intramuscular fat

18 Muscle Quantification on HR-pQCT Soft Tissue Evaluation Tool

19 HR-pQCT Muscle Segmentation Seed volume identities: Fat threshold: mgha/cm 3 Muscle threshold: to mgha/cm 3 Algorithm Seed volumes Planted Unconnected volumes removed Seed volumes Iteratively expanded Areas of overlap undefined Areas of overlap mgha/cm 3 Muscle / Fat FINAL IMAGE 20 Iterations

20 Comparison with pqct Post-menopausal women (n=45) Age (years) 74.6 (8.5) Height (m) 1.62 (0.07) Weight (kg) 68.0 (11.6) BMI (kg/m 2 ) 25.9 (4.3) TUG (seconds) 11.3 (3.4) Grip Strength (kg) 24.0 (6.0) pqct HR-pQCT HR-pQCT (66% Site) (HA calibration) (HU calibration) MD 70.0 (5.0) mg/cm (4.7) mg/cm (13.4) HU MCSA 5738 (899) mm (242) mm (250) mm 2 Muscle Volume (2.1) cm (2.1) cm 3

21 pqct 66% Muscle Density (mg/cm 3 ) pqct 66% Muscle Area (mm 2 ) Relationship between pqct (prox) & HR-pQCT Muscle (distal) Measurement R 2 P-val B Beta Int MD (mg/cm 3 ) < (0.089,0.283) MCSA (mm 2 ) < (1.227,3.231) Simple linear regression analysis HR-pQCT 22.5 mm site Muscle Density (Houndsfield Units) HR-pQCT 22.5 mm site Muscle Area (mm 2 )

22 XtremeCT2 Calf Imaging

23 ~ 66% Site Muscle Analysis on XtremeCT2

24 ~ 66% Site Muscle Analysis on XtremeCT2 Sample Name Site MV cm 3 MV/TV MD mg/cm 3 Fat Density mg/cm 3 Calf_test#003 Tibia L Calf_test#001 Tibia L Calf_test#004 Tibia L Calf_test#005 Tibia L Calf_test#006 Tibia L Calf_test#006 Radius R

25 Ultrasound Achilles Tendon Imaging GE Logiq E Portable USI Systems (12 MHz, linear transducer B- mode) OsiriX Manual contouring of Achilles Tendon CSA Images obtained from transverse scan Tendon CSA obtained values averaged between three scans

26 Achilles Tendon on HR-pQCT Standard HR-PQCT distal tibia scan 22.5 mm site Soft Tissue Analysis Applied a) b) c) A) Semi-automatic contour of the limb. B) Soft-tissue contours generated for semi-automatic threshold algorithm. C) Manually edited contours around Achilles tendon.

27 Difference HR-pQCT vs. Ultrasound TCSA (cm 2 ) Comparison of HR-pQCT and Ultrasound-derived Tendon CSA SD Mean Women and Men (>50 years) Mean Age = 63.2 years Mean BMI = 24.9 kg/m SD TCSA Measurements Variable N Mean SD HR-pQCT Ultrasound Average of HR-pQCT and Ultrasound Tendon CSA (cm 2 )

28 Mean Ultrasound Tendon CSA (cm 2 ) Comparison of HR-pQCT and Ultrasound-derived Tendon CSA HR-pQCT vs Ultrasound TCSA Correlation Plot Correlation: r = 0.703, p=0.002 ICC (2,1) Using Consistency Definition ICC LCI UCI Single Measure Average Measur Mean HR-pQCT Tendon CSA (cm 2 )

29 T2 Relaxation (ms) MRI & QCT-Compatible Muscle Calibration Phantom T2 Relaxation (ms) Density (mg/cm 3 ) Phantom Properties Fatty Muscle Average Muscle Lean Muscle [CuCl 2 ] 4.00 mm mm mm [EDTA] 0.73 mm 0.03 mm 0.01 mm T2 relaxation time ms ms ms Density 65 mg/cm mg/cm mg/cm CuCl 2 Concentration (mmol/l) CuCl2 Concentration (mmol/l) D = 0.27[CuCl 2 ] , R 2 = 0.84, p = 0.01 T2 = ln[CuCl 2 ] , R 2 =0.91, p<0.01 T2 = 5.72 ln[edta]+54.47, R 2 =0.86, p< EDTA Concentration (mmol/l)

30 Odds for a Fragility Fracture Effect of Muscle Fractures Conditional on Frailty CaMos Frailty Index Johnson-Neyman technique Identified CFI values: 0.05 to 0.13 as region in which effect of Muscle Density Fractures were significant Vertical lines = 95% confidence intervals Points = Point estimate Muscle Cross- Sectional Area & Muscle Mass: Frailty showed no moderation effect

31 Canadian Musculoskeletal Imaging Network Calgary, AB U of C, Foothills Hospital (hr-pqct, pmri, DXA) Vancouver, BC CHHM, VCH (hr-pqct, pqct, DXA) Saskatoon, SK U of Saskatchewan (hr-pqct, pqct, DXA) Hamilton Coordinating Centre Adachi Medicine, McMaster (pqct, pmri, DXA) Hamilton, ON St. Peter s, HHS (DXA, pmri planned) Ottawa, ON CHEO, U of Ottawa (pqct, DXA) Montreal, QC Shriner s Hospital (pqct, DXA) Kingston, ON Queen s U, HMRC (pqct, DXA) Toronto, ON TGH, JDMI, UHN (hr-pqct, pqct pmri, DXA)

32 Participation from over 12 academic institutions and over 16 Canadian investigators across five provinces in Canada

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