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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. kpopuri@sfu.ca

-  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