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EVOLUTION OF BONE DENSITOMETRY
        NOVEL DXA USES

          M h 8th, 2012
          March
    ISCD 2012: Los Angeles, CA

          Mark Punyanitya
        Biomedical Engineer
TYPES OF FAT
  Apple shape vs. Pear shape                                                  Subcutaneous Adipose Tissue (SAT)

                                                                             S b t
                                                                              Subcutaneous f t found underneath the skin,
                                                                                             fat f  d d         th th ki
                                                                              which may cause dimpling and cellulite

                                                            Above the
                                                                             Fat accumulated in the lower body (the pear
                                                              waist           shape) is subcutaneous
                                                                                  p )
                                                                Below the
                                                                  waist



                                                                              Visceral Adipose Tissue (VAT)
                                                                             Also known as, intra-abdominal fat, belly fat, beer
                                                                              belly, central adiposity

Apple shape
                                                                             Visceral fat pads all internal vital organs such as
                                      Pear shape
•More visceral fat                    •Less visceral fat                      stomach, kidney, heart and also pancreas
•Higher risk of weight‐               •Lower risk of weight‐
related health                        related health                         Fat in the abdominal area (the apple shape) is
problems                              problems                                largely visceral
 Source: GSK education material
 S       GSK d      i       i l
 http://www.alli.co.uk/How‐alli‐works/How‐visceral‐fat‐works/                Metabolically active
VISCERAL ADIPOSE TISSUE (VAT)
• VAT (fat in and around
  abdominal organs) has been
  shown to be a risk factor for all
  cause mortality in men1

• VAT is a unique pathogenic fat
             unique,
  depot2 associated with
  metabolic risk factors
  (triglycerides, cholesterol,
  (triglycerides cholesterol
  fasting glucose, hypertension)
  and CVD
 1Kuk JL, et al Visceral fat is an independent predictor of all-
 cause mortality in men. Obesity. 2006;14(2):336-41.

 2Fox  CS, et al Abdominal visceral and subcutaneous adipose
 tissue compartments: association with metabolic risk factors in
 the Framingham Heart Study. Circulation. 2007 Jul 3;116(1):39-
 48.
VISCERAL FAT AND METABOLIC RISK
                   Key Points
                Recent study of more than 3000
                 participants drawn from the
                 Framingham Heart Study showed
                SAT and VAT are correlated with
                 metabolic risk factors
                VAT more strongly associated with
                 an adverse metabolic risk profile
                GR = 4.7/SD (Females)
                G = 4.2/SD (
                 GR     /S (Males)
                                 )


               .

                     Fox CS et al. (2007) Circulation 116 39-48
Visceral
Adipose
Tissue




Subcutaneous      Residual
Adipose             Tissue
Tissue
Tiss e         Compartment
WHOLE-BODY
WHOLE BODY MRI ANALYSIS
Visceral
  Adipose
  Tissue




                             Muscle
Subcutaneous
                             Tissue
Adipose
Tissue

                  Residual
                    Tissue
                    Tiss e
               Compartment
Visceral
       Adipose
       Tissue


                                Muscle
                                Tissue



Subcutaneous
Adipose
Tissue
                     Residual
                     Resid al
                       Tissue
                  Compartment
RELIABILITY MEASURE FOR MRI
                    ICC    CV
 Skeletal Muscle    0.99   2-5%
 Subcutaneous AT    0.99   2-5%
 Visceral AT
 Vi     l           0.95   2-5%
 Intermuscular AT   0.97
                    0 97   5 8%
                           5-8%
SENSITIVITY MEASURE FOR MRI
MRI    Baseline
         ase e     S of
                   SD o      Individual
                               d dua      G oup
                                          Group
(kg)    (mean)    changes      95% CI     95% CI
                  (1 year)                (N=20)
SM       18.6
         18 6       0.40
                    0 40       0.82
                               0 82        0.19
                                           0 19
TAT      26.8       1.00       2.06        0.47
SAT      24.0
         24 0       0.90
                    0 90       1.85
                               1 85        0.43
                                           0 43
VAT      1.9        0.20       0.41        0.09
IMAT     1.08
         1 08       0.10
                    0 10       0.21
                               0 21        0.05
                                           0 05
MRI Analysis
    •Tissues were segmented 
    by trained technicians using 
    commercially available 
    image analysis software. 
    •Analysis time: 24 hours for 
          y
    subcutaneous adipose 
    tissue, skeletal muscle, 
    Visceral adipose tissue, 
                p           ,
    Bone+organ, Intramuscular 
    adipose tissue, lung.

‐Shen W., et al., Curr Opin Clin Nutr Metab Care.
‐2006;8:595‐601
The % difference between Vgap and Vtrue was
      generally smaller with the decrease of gap size

                    2 cm gap            3 cm gap              4 cm gap     5 cm gap
  Acquisition     40-50 minutes      35-40 minutes           30 minutes    25 minutes
  time
  Analysis
     a ys s         12 hours             8 hours
                                            ou s              6 5 ou s
                                                              6.5 hours     5 hours
                                                                               ou s
  time
  SM             0.30%±0.43% 0.41%±0.35% 0.59%±0.63% 1.04%±0.77%*
                         *             *                *
 SAT             0.26%±0.23% 0.53%±0.45% 0.59%±0.49% 0.85%±0.86%*
                         *             *                *
 VAT             3.14%±2.99% 5.23%±6.01% 8.14%±8.15% 9.70%±8.58%*
                         *             *                *
 IMAT            3.06%±2.41% 4.75%±4.48% 6.93%±7.30% 9.55%±8.77%*
 Studies will require 2 % more subjects if every 5 cm protocol is used in 5 to 17 
                         *             *                *
   year old subjects and 8‐10 % more subjects in 5 to 10 year old prepubertal 
   children for equivalent power as the continuous every‐cm protocol in measuring 
    hild    f      i l t            th     ti                    t li          i
   VAT and IMAT.
                        ‐ Shen W., et al., Int J Pediatric Obesity. 2010
Pearson correlations between VAT volume and
        VAT areas for individual transverse slices

                                              Correlation Coefficients


                             -10 cm   -5 cm      L4-L5    + 5 cm + 10 cm         + 15 cm



Men     Abdominal VAT                 0.843      0.899     0.951      0.966           0.924


        Abdominopelvic VAT   0.857    0.889      0.919     0.950      0.961           0.917


Women   Abdominal VAT                 0.908      0.929     0.972      0.961           0.822



        Abdominopelvic VAT   0.856    0.930      0.936     0.964      0.951           0.821



                                      ‐ Shen W et al., Am J Clin Nutr 2004;80:271‐8
Group                                        Glu       Insulin       TG         HDL         SBP        DBP
Men           Abdominal VAT                 .211       .505          .361       -.242       .312       .318
(n= 283)      Abdominopelvic VAT            .217       .522          .356       -.255       .309       .316
              -5 cm                         .186       .389**        .272**     -.194       .244**     .264
              L4-L5                         .193       .384**        .276**     -.162**     .277       .266**
              +5 cm                         .187       .458**        .354       -.235       .307       .306
              +10 cm
               10                           .210       .520          .401
                                                                     .401*      -.271*
                                                                                 .271       .306       .313
              +15 cm                        .201       .522          .332       -.238       .295       .313
Women         Abdominal VAT                 .218       .569          .397       -.383       -.054      .104
(n = 411)     Abdominopelvic VAT            .222
                                             222       .558
                                                        558          .398
                                                                      398       -.385
                                                                                  385       -.051
                                                                                              051      .110
                                                                                                        110
              -5 cm                         .192       .547          .386       -.386       -.072      .069
              L4-L5                         .161**     .569          .369       -.350**     -.054      .139
              +5 cm                         .219
                                             219       .562
                                                        562          .392
                                                                      392       -.392
                                                                                - 392       -.060
                                                                                            - 060      .076
                                                                                                        076
              +10 cm                        .230       .514**        .385       -.348**     -.062      .083
              +15 cm                        .220       .467**        .305**     -.299**     .013       .118
*, significantly higher (P < 0.05) than abdominal VAT; **, significantly lower (P < 0.05) than abdominal VAT.
                                       ‐Shen W., et al., Int J Obesity, 2007,31:763‐9
How CoreScan works
•    Key Differentiator: Separates out SAT and VAT

1. Start with total fat
      iDXA distinguishes between fat, lean and bone through dual
       energy measurements
      Excellent image resolution helps enable accurate tissue
       characterization


2.    Calculate SAT
      Utilize iDXA to measure SAT layer thickness at sides of
       android region
      CoreScan maps the total SAT layer around android region

                                                                    SAT inner wall
3.    Total fat – SAT = VAT                                         SAT outer wall
CoreScan: Reproducible


• Defined region of measurement ‐ Android
• Automated definition of region – based off
  Automated definition of region – based off 
  bone landmarks on the body
• Consistent method of acquisition
CoreScan: Reproducible
            Android Region



Standard region of interest for iDXA body 
composition
    p
Base of the ROI located at top of pelvis
Height (H) = 20% of distance from top of 
pelvis to base of skull 
pelvis to base of skull
Android region contains high proportion of 
visceral fat
Relatively little bone in android region
CoreScan: Accuracy

   • Validated in clinical trial*
   • High degree of correlation with CT
   • On average difference between iDXA
     On average difference between iDXA 
        and CT ~60g
   • 95% of subjects were within a range of                                              CT image of visceral fat from 
                                                                                         subject (42 year old male; 
        16‐96cm3 difference between measuring                                            BMI = 26.2 kg/m2)
                                                                                       Image courtesy of Dr. Sanjiv Kaul
                                                                                       I               f D S ji K l
        with CT and iDXA



* Kaul et al. Dual X‐Ray Absorptiometry for Quantification of Visceral Adipose Tissue. Advance online publication 26 January 2012.
CoreScan: Accuracy
                                         Analysis on OHSU Data

                                                                                                  OHSU CT vs. iDXA VAT Volume
                                                                                                            All Subjects
                                                                                       5000

        Excellent Correlation*
                                                                                       4000

     Gender         SEE          r2




                                                                                 m³)
                                                                  CT VA Volume (cm
                                                                                       3000
    Females  0.960 190.5
    Males    0.953 221.6


                                                                      AT
                                                                                       2000


    Combined 0.958 209.4                                                               1000



                                                                                          0
                                                                                              0      1000    2000          3000   4000   5000
                                                                                                        iDXA VAT Volume (cm³)
                                                                                                                    data     ID




* Kaul et al. Dual X‐Ray Absorptiometry for Quantification of Visceral Adipose Tissue. Advance online publication 26 January 2012.
SUMMARY
• Further studies are needed to determine
  whether VF estimation offers incremental
  value to other more standard measures of
  metabolic and cardiovascular risk in
  patients.
  patients
VISCERAL ADIPOSE TISSUE
VISCERAL ADIPOSE TISSUE (VAT)
            ROI DEFINITION




Regions are automatically placed by the software
•Outer region extends across entire abdomen
 Outer
•Middle region extends across visceral cavity including
abdominal wall
•Inside region extends across visceral cavity just inside abdominal
wall
DXA VAT vs. VAT by CT
                                   y

                                                                      •Linear Relation
                                                                        i       l i
                                                                      •High Correlation
                                                                      •Low SEE vs. CT
                                                                      VAT by an Expert
                                                                      Reader




Micklesfield et al, Dual-Energy X-Ray Performs as Well as Clinical Computed Tomography
for the Measurement of Visceral Fat, Advance online publication 12 January 2012
CONCLUSION
• If these findings are supported by similar
  results in other populations, DXA-VAT
  may become a useful alternative to CT
  and MRI for the estimation of VAT in both
  clinical and research settings
                         settings.
SUMMARY OF NEW
   BODY COMPOSITION FEATURES

The new VAT Application, reference values, and
reporting enhancements should be helpful in the
  p      g                                        p
evaluation of a wide variety of abnormalities involving fat
mass, lean mass, and bone, for establishing entry
criteria into clinical trials and for other clinical research
                       trials,              clinical, research,
and epidemiological uses.
Mark Punyanitya
Biomedical Engineer
Bi    di l E i
Director, Image Reading Center

Phone:       (646) 736-2487
Email:       mark@imagereadingcenter.com
Web:         www.imagereadingcenter.com
             www imagereadingcenter com

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ISCD 2012 Punyanitya DXA-VAT Presentation

  • 1. EVOLUTION OF BONE DENSITOMETRY NOVEL DXA USES M h 8th, 2012 March ISCD 2012: Los Angeles, CA Mark Punyanitya Biomedical Engineer
  • 2.
  • 3.
  • 4.
  • 5. TYPES OF FAT Apple shape vs. Pear shape Subcutaneous Adipose Tissue (SAT)  S b t Subcutaneous f t found underneath the skin, fat f d d th th ki which may cause dimpling and cellulite Above the  Fat accumulated in the lower body (the pear waist shape) is subcutaneous p ) Below the waist Visceral Adipose Tissue (VAT)  Also known as, intra-abdominal fat, belly fat, beer belly, central adiposity Apple shape  Visceral fat pads all internal vital organs such as Pear shape •More visceral fat •Less visceral fat stomach, kidney, heart and also pancreas •Higher risk of weight‐ •Lower risk of weight‐ related health  related health   Fat in the abdominal area (the apple shape) is problems problems largely visceral Source: GSK education material S GSK d i i l http://www.alli.co.uk/How‐alli‐works/How‐visceral‐fat‐works/  Metabolically active
  • 6.
  • 7. VISCERAL ADIPOSE TISSUE (VAT) • VAT (fat in and around abdominal organs) has been shown to be a risk factor for all cause mortality in men1 • VAT is a unique pathogenic fat unique, depot2 associated with metabolic risk factors (triglycerides, cholesterol, (triglycerides cholesterol fasting glucose, hypertension) and CVD 1Kuk JL, et al Visceral fat is an independent predictor of all- cause mortality in men. Obesity. 2006;14(2):336-41. 2Fox CS, et al Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007 Jul 3;116(1):39- 48.
  • 8. VISCERAL FAT AND METABOLIC RISK Key Points  Recent study of more than 3000 participants drawn from the Framingham Heart Study showed  SAT and VAT are correlated with metabolic risk factors  VAT more strongly associated with an adverse metabolic risk profile  GR = 4.7/SD (Females)  G = 4.2/SD ( GR /S (Males) ) . Fox CS et al. (2007) Circulation 116 39-48
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14. Visceral Adipose Tissue Subcutaneous Residual Adipose Tissue Tissue Tiss e Compartment
  • 15.
  • 17.
  • 18.
  • 19.
  • 20. Visceral Adipose Tissue Muscle Subcutaneous Tissue Adipose Tissue Residual Tissue Tiss e Compartment
  • 21. Visceral Adipose Tissue Muscle Tissue Subcutaneous Adipose Tissue Residual Resid al Tissue Compartment
  • 22. RELIABILITY MEASURE FOR MRI ICC CV Skeletal Muscle 0.99 2-5% Subcutaneous AT 0.99 2-5% Visceral AT Vi l 0.95 2-5% Intermuscular AT 0.97 0 97 5 8% 5-8%
  • 23. SENSITIVITY MEASURE FOR MRI MRI Baseline ase e S of SD o Individual d dua G oup Group (kg) (mean) changes 95% CI 95% CI (1 year) (N=20) SM 18.6 18 6 0.40 0 40 0.82 0 82 0.19 0 19 TAT 26.8 1.00 2.06 0.47 SAT 24.0 24 0 0.90 0 90 1.85 1 85 0.43 0 43 VAT 1.9 0.20 0.41 0.09 IMAT 1.08 1 08 0.10 0 10 0.21 0 21 0.05 0 05
  • 24. MRI Analysis •Tissues were segmented  by trained technicians using  commercially available  image analysis software.  •Analysis time: 24 hours for  y subcutaneous adipose  tissue, skeletal muscle,  Visceral adipose tissue,  p , Bone+organ, Intramuscular  adipose tissue, lung. ‐Shen W., et al., Curr Opin Clin Nutr Metab Care. ‐2006;8:595‐601
  • 25. The % difference between Vgap and Vtrue was generally smaller with the decrease of gap size 2 cm gap 3 cm gap 4 cm gap 5 cm gap Acquisition 40-50 minutes 35-40 minutes 30 minutes 25 minutes time Analysis a ys s 12 hours 8 hours ou s 6 5 ou s 6.5 hours 5 hours ou s time SM 0.30%±0.43% 0.41%±0.35% 0.59%±0.63% 1.04%±0.77%* * * * SAT 0.26%±0.23% 0.53%±0.45% 0.59%±0.49% 0.85%±0.86%* * * * VAT 3.14%±2.99% 5.23%±6.01% 8.14%±8.15% 9.70%±8.58%* * * * IMAT 3.06%±2.41% 4.75%±4.48% 6.93%±7.30% 9.55%±8.77%*  Studies will require 2 % more subjects if every 5 cm protocol is used in 5 to 17  * * * year old subjects and 8‐10 % more subjects in 5 to 10 year old prepubertal  children for equivalent power as the continuous every‐cm protocol in measuring  hild f i l t th ti t li i VAT and IMAT. ‐ Shen W., et al., Int J Pediatric Obesity. 2010
  • 26. Pearson correlations between VAT volume and VAT areas for individual transverse slices Correlation Coefficients -10 cm -5 cm L4-L5 + 5 cm + 10 cm + 15 cm Men Abdominal VAT 0.843 0.899 0.951 0.966 0.924 Abdominopelvic VAT 0.857 0.889 0.919 0.950 0.961 0.917 Women Abdominal VAT 0.908 0.929 0.972 0.961 0.822 Abdominopelvic VAT 0.856 0.930 0.936 0.964 0.951 0.821 ‐ Shen W et al., Am J Clin Nutr 2004;80:271‐8
  • 27. Group Glu Insulin TG HDL SBP DBP Men Abdominal VAT .211 .505 .361 -.242 .312 .318 (n= 283) Abdominopelvic VAT .217 .522 .356 -.255 .309 .316 -5 cm .186 .389** .272** -.194 .244** .264 L4-L5 .193 .384** .276** -.162** .277 .266** +5 cm .187 .458** .354 -.235 .307 .306 +10 cm 10 .210 .520 .401 .401* -.271* .271 .306 .313 +15 cm .201 .522 .332 -.238 .295 .313 Women Abdominal VAT .218 .569 .397 -.383 -.054 .104 (n = 411) Abdominopelvic VAT .222 222 .558 558 .398 398 -.385 385 -.051 051 .110 110 -5 cm .192 .547 .386 -.386 -.072 .069 L4-L5 .161** .569 .369 -.350** -.054 .139 +5 cm .219 219 .562 562 .392 392 -.392 - 392 -.060 - 060 .076 076 +10 cm .230 .514** .385 -.348** -.062 .083 +15 cm .220 .467** .305** -.299** .013 .118 *, significantly higher (P < 0.05) than abdominal VAT; **, significantly lower (P < 0.05) than abdominal VAT. ‐Shen W., et al., Int J Obesity, 2007,31:763‐9
  • 28.
  • 29. How CoreScan works • Key Differentiator: Separates out SAT and VAT 1. Start with total fat  iDXA distinguishes between fat, lean and bone through dual energy measurements  Excellent image resolution helps enable accurate tissue characterization 2. Calculate SAT  Utilize iDXA to measure SAT layer thickness at sides of android region  CoreScan maps the total SAT layer around android region SAT inner wall 3. Total fat – SAT = VAT SAT outer wall
  • 30. CoreScan: Reproducible • Defined region of measurement ‐ Android • Automated definition of region – based off Automated definition of region – based off  bone landmarks on the body • Consistent method of acquisition
  • 31. CoreScan: Reproducible Android Region Standard region of interest for iDXA body  composition p Base of the ROI located at top of pelvis Height (H) = 20% of distance from top of  pelvis to base of skull  pelvis to base of skull Android region contains high proportion of  visceral fat Relatively little bone in android region
  • 32. CoreScan: Accuracy • Validated in clinical trial* • High degree of correlation with CT • On average difference between iDXA On average difference between iDXA  and CT ~60g • 95% of subjects were within a range of  CT image of visceral fat from  subject (42 year old male;  16‐96cm3 difference between measuring  BMI = 26.2 kg/m2) Image courtesy of Dr. Sanjiv Kaul I f D S ji K l with CT and iDXA * Kaul et al. Dual X‐Ray Absorptiometry for Quantification of Visceral Adipose Tissue. Advance online publication 26 January 2012.
  • 33. CoreScan: Accuracy Analysis on OHSU Data OHSU CT vs. iDXA VAT Volume All Subjects 5000 Excellent Correlation* 4000 Gender SEE r2 m³) CT VA Volume (cm 3000 Females 0.960 190.5 Males 0.953 221.6 AT 2000 Combined 0.958 209.4 1000 0 0 1000 2000 3000 4000 5000 iDXA VAT Volume (cm³) data ID * Kaul et al. Dual X‐Ray Absorptiometry for Quantification of Visceral Adipose Tissue. Advance online publication 26 January 2012.
  • 34. SUMMARY • Further studies are needed to determine whether VF estimation offers incremental value to other more standard measures of metabolic and cardiovascular risk in patients. patients
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  • 37. VISCERAL ADIPOSE TISSUE (VAT) ROI DEFINITION Regions are automatically placed by the software •Outer region extends across entire abdomen Outer •Middle region extends across visceral cavity including abdominal wall •Inside region extends across visceral cavity just inside abdominal wall
  • 38. DXA VAT vs. VAT by CT y •Linear Relation i l i •High Correlation •Low SEE vs. CT VAT by an Expert Reader Micklesfield et al, Dual-Energy X-Ray Performs as Well as Clinical Computed Tomography for the Measurement of Visceral Fat, Advance online publication 12 January 2012
  • 39. CONCLUSION • If these findings are supported by similar results in other populations, DXA-VAT may become a useful alternative to CT and MRI for the estimation of VAT in both clinical and research settings settings.
  • 40. SUMMARY OF NEW BODY COMPOSITION FEATURES The new VAT Application, reference values, and reporting enhancements should be helpful in the p g p evaluation of a wide variety of abnormalities involving fat mass, lean mass, and bone, for establishing entry criteria into clinical trials and for other clinical research trials, clinical, research, and epidemiological uses.
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  • 50. Mark Punyanitya Biomedical Engineer Bi di l E i Director, Image Reading Center Phone: (646) 736-2487 Email: mark@imagereadingcenter.com Web: www.imagereadingcenter.com www imagereadingcenter com