talk 2 ppt for handout · as an expedient nutritional assessment tool in research and clinical...
TRANSCRIPT
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USE OF COMPUTERIZED TOMOGRAPHY AS AN EXPEDIENT NUTRITIONAL ASSESSMENT TOOL IN RESEARCH AND CLINICAL SETTINGS
CARLA PRADO, PHD, RD ASSISTANT PROFESSOR & CAIP CHAIR IN NUTRITION, FOOD & HEALTH DIRECTOR, HUMAN NUTRITION RESEARCH UNIT DEPARTMENT OF AGRICULTURAL, FOOD AND NUTRITIONAL SCIENCE UNIVERSITY OF ALBERTA, CANADA WWW.HNRU.ALES.UALBERTA.CA WWW.DRCARLAPRADO.COM @UOFANUTRITION
Talk developed in collaboration with Dr. V. Baracos, University of Alberta
LEARNING OBJECTIVES
• To review the theoretical background related to computerized tomography (CT) body composition assessment
• To discuss the practicality and procedures of this technique
• To review the application and interpretation of CT body composition data
Routine Assessment
of Low Muscle Mass
Value
Accuracy/Precision
Practicality
Technological developments
Applicability
Selected body composition components measured by imaging techniques
Prado & Heymsfield J Parenter Enteral Nutr 2014;38:940-953
Copyright © by The American Society for Parenteral and Enteral Nutrition
Subcutaneous adipose tissue
Visceral adipose tissue
Intermuscular adipose tissue
Skeletal muscle
DXA CT
CT SCAN - THE PHYSICS Vastly simplified, CT scanners emit x-rays that pass through the body and are detected by a sensor. A computer records the amount of x-radiation that has passed through the body and both the rotational and vertical positions of the x-ray tube at each reading. Through complex mathematical analysis, a 2-dimensional representation is made of the body.
CT GRAY-SCALE RECONSTRUCTION
• The computer constructs a graphic image, assigning a Hounsfield unit number to represent the radio-density at each point.
• The number for each point in the image (pixel) is shown as a level of gray (from black to white).
• Position of image and thickness of image are indicated
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Adipose tissue [-190,-30] HU
Skeletal muscle [-29,+150] HU
Bone
-190 -30 150 0 HU
The Hounsfield unit (HU) scale is a linear transformation of the linear attenuation coefficient measurement of a tissue in which the radiodensity of distilled water at standard pressure and temperature is defined as zero HU and the radiodensity of air at STP is defined as -1000 HU. Bone +400 HU Muscle +40 HU Fat -120 HU
Intramuscular adipose
Association Between Whole Body Tissue Volume (L) and Single Abdominal Surface Area (cm2)
Shen, W. et al. J Appl Physiol 97:2333-2338 2004
Ross & Janssen. CT and MRI. In: Human Body Composition, 2005:p.89
TOTAL LUMBAR CROSS – SECTIONAL AREA IS THE CONVENTION
Total muscle area • Cm2 ; Cm2 /m2
• Correlates with whole body values
• Accepted convention in >90% of publications
Single muscle approach • e.g. psoas major,
pectoralis, erector spinae
• Not validated, not representative, high error
Anatomic annotations: Learn relevant anatomy & when in doubt consult a radiologist Skeletal muscle area Muscle radiation attenuation & intermuscular adipose tissue Visceral adipose tissue Subcutaneous adipose tissue
SUBCUTANEOUS ADIPOSE TISSUE VISCERAL ADIPOSE TISSUE
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Rectus abdominis, oblique and lateral abdominal, psoas, quadratus lumborum, paraspinal
SKELETAL MUSCLE
-190 -150 -110 -70 -30 10 50 90 130 Hounsfield Units (HU)
-190 -150 -110 -70 -30 10 50 90 130 Hounsfield Units (HU)
A
B
C
D
E
F
G
H
A,B contrast enhanced CT images of paraspinal muscles, C,D annotated CT images, and E,F pie charts with accompanying G,H histograms of radiation attenuation showing % total tissue area within the ranges of adipose tissue [light blue, -190 to -30 Hounsfield Units, HU], normal attenuation muscle [red, +30 to +150 HU], and abnormal (reduced) attenuation muscle in two ranges [dark blue, -29 to 0 HU; yellow, +1 to +29 HU].
Muscle Radiation Attenuation
Prado et al. Proc Nut Soc. 2016 v.75(2):188
Normal
Reduced
AT
PRACTICALITY: PROCEDURES Requirements:
• Appropriate software: tissue marking and automated computation
• Personnel trained to use the software • Image availability from clinical library of diagnostic
images
Procedures: • Find the landmark of interest and retrieve images for
analysis (DICOM format) • Browser used to locate and retrieve images • Uploading images in appropriate software for tissue
analysis • Assess muscle area
LANDMARKING
https://www.youtube.com/watch?v=a9crLgKsdOA
SLICEOMATIC
https://www.youtube.com/watch?v=KJrsQ_dg5mM
OSIRIX
https://www.youtube.com/watch?v=s1eJSK_CWco
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TECHNOLOGICAL DEVELOPMENTS: AUTOMATIC SEGMENTATION
• Automated method for segmenting muscle, visceral and subcutaneous adipose tissues, taking the approach of shape modeling for the analysis of skeletal muscle.
Popuri K et al. Body Composition Assessment in Axial CT Images Using FEM-Based Automatic Segmentation of Skeletal Muscle. IEEE Trans Med Imaging. 2016;35:512-20. [email protected]
- Automated vs. manual methods: % CV (~2%) on unselected images - Similar to inter-and intra-observer CV for manual segmentation
Eliminates the lack of a simple report summary derived from the images and provides relevant, ready to use information to clinicians
High Jaccard score (% overlap between automatic and manual segmentations) OTHER LANDMARKS OF INTEREST
V Baracos. Body Composition Analysis Using CT imaging Manual. Univ. of Alberta
T4
Wieland et al. Clin Cancer Res 2007 1:4984.
APPLICATION & INTERPRETATION OF THE DATA
APPLICABILITY
Identify and monitor sarcopenia in a large number of patients, including repeated measurements over time.
Early detection and intervention of sarcopenia.
Compare sarcopenia among different cancer groups.
Prevent chemotherapy toxicity caused by overdosing the sarcopenic patient.
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Population distribution of the body composition features
DEMOGRAPHICS: WHAT IS NORMAL?
FEATURE DISTRIBUTION; MALE; LUNG CANCER; CAUCASIAN; CANADA
Muscularity (muscle area/height2) sex specific A continuous distribution
0.5
1.5
2.5
3.5
4.5
0 25 50 75 100
Low muscle mass (Sarcopenia): a low level of muscle, characterized by statistically significant* increase in health risk (mortality, toxicity, physical disability).
*A cut point test provides a simplified clinical score e.g. sarcopenic YES/NO
Haz
ard
ratio
, for
dea
th
*
* CLINICAL OUTCOMES: SELECTED DATA
Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastro-intestinal tracts: a population-based study. Prado CM et al Lancet Oncol. 2008;9:629-35.
• All patients of BMI > 30 • N=250, independent of
age, disease stage and performance status
• 11 months vs 21 months median survival
Low Muscle Mass Multivariate Hazard Ratio for death, many studies
0 0.5 1 1.5 2 2.5 3 3.5
Camus DLBL
Fogelman Pancreas
Miyamoto Colon
Psutka Cystectomy
Tan Pancreas
Van Vledder Colon
Normal Sarcopenic
*** ** ***
** *
***
Multivariate p < 0.05 *, p < 0.005 **, p < 0.0005***
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Forest plots of HR for OS: N=37 studies; 7779 patients
Shachar et al Europ J Cancer, 2016; 57:58–67
% o
f pat
ient
s w
ith d
ose-
limiti
ng to
xici
ty
Low Muscle Mass
High Lean Mass
0
10
20
30
40
50
60
70
80
90
100
5FU
Capecitabine
Adjuvant FEC
Sorafenib
Sorafenib
Sunitinib
Vandetanib
Fluoropyrimidine
Imatinib
ECX & CF
Higher Prevalence of Dose Limiting Toxicity
Prado et al. Proc Nut Soc. 2016 v.75(2):188 FEC = 5FU, Epirubicin, Cyclophosphnide ECX & CF = Epirubicin, Cisplatin, Capecitabine Fluoropyrimidine = 5FU or Capecitabine
Skeletal muscle radiodensity is an independent predictor of response and outcomes in follicular lymphoma treated with chemo-immunotherapy Chu M et al. PloS1 2015 31:1539-47
Overall survival, months
Low Muscle Radiodensity Multivariate Hazard Ratio for death, Confirmed in many studies
Multivariate p < 0.05 *, p < 0.005 **, p < 0.0005***
0 0.5 1 1.5 2 2.5 3 3.5
Martin - Lung GI
Chu - FL
Knijnenburg - RCC
Okamura Pancr
Hamaguchi - HCC
Tamandl - gas/esoph
Fujiwara - HCC
Normal Fatty
***
***
**
*** ***
*** **
• Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials).
• CT Body Composition Analysis: direct association of sarcopenia with study outcomes and other variables
ADDITIONAL MEASUREMENT
Baseline Day 84 Day 147
CT CT CT
83% images of patients with tumor response assessment were available
MENAC: The Multimodal Exercise/Nutrition/Anti-inflammatory treatment for Cachexia trial ¢ Large-scale, open, randomized phase III study comparing multimodal intervention versus standard cancer care. � oral nutritional supplements, celecoxib and physical
exercise
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Body Composition Clinical Guidelines
39
GET THE CONVERSATION STARTED!
Access opportunities Engage colleagues Harvest resources Operationalize procedures Implement
CONCLUSIONS - Assessment of high resolution CT images can be done
with high precision and specificity
• Validated • Evaluate large number of patients including repeated
measures over time • Do not required specialized skills • Feasible with upcoming improvements (automated
software) • Strategically incorporated in the nutrition care process
COLLEAGUES: Dr. Vickie Baracos Dr. Cristina Gonzalez Dr. Marina Mourtzakis Dr. Sunita Gosh Dr. Arya Sharma Jessica Lieffers
ACKNOWLEDGMENTS
PRADO’S LAB Dr. Sarah Elliott Adele Gagon Carlene Johnson Stoklossa Taiwo Olobatuyi Camila Orsso Leticia Pereira Camila Pinto Sarah Purcell Amanda Purkiss Claire Trottier Jingjie Xiao