Ultimate In Vivo Imaging and Automatic DXA Analysis for Longitudinal Studies

DXA(Dual energy X-ray Absorptiometry) as Solution

3

VET DXA New Gold Standard

1. Why Osteosys?

2. What is DXA?

3. iNSiGHT: Special Feature

4. iNSiGHT: Imaging Analysis

Why Osteosys?

COMPANY HISTORY: ENTHUSIASTIC RESEARCHER

An enthusiastic young professor wanted to make a “better product for better life”for the people who were suffered by osteoporosis.To realize his dream, our strong R&D center launches a new product every 2 years.

1998 2000 2001 2004 2005 2008 2011 2013 2015 2018

Studied BMD Technology at small Lab. In KonKukUniversity

Established Osteosys with1st Gen. QUS

Launched 1st Gen. pDXA(Peripheral Cone Beam DXA)

Launched2nd Gen. QUS (Waterless probe)

Launched1st Central DXA(First pencil

DXA)

Launched 2nd Gen. Pencil beam

beam table type DXA(compact design& fold wing bedDown)

Launched 2nd Gen. pDXA

Launched 1st Gen. Whole body DXA(with Body composition & Assessment)

Launched1st GenCentral smart Fan beam DXA

Launched 3rd GenQUS(Mobile accessibility)

2019

Animal DXA

FAST GROWING: BMD Market Share (2018)

China : Approx. 60% (QUS)

Color distribution in Korea

> > > > >> >>

Korea market : 80%

With the good quality and cost-effective BMD devices,Osteosys is dominant in the domestic market, and main player in Chinese market.

7

Full Line Up BMD of Osteosys

QUS

PDXA

DXAPencil beam

DXAFan beam

SHARE IT WORLDWIDE

We would like to share our BMD with the people around the world.

more than 100 countries 130 worldwide sales networks

7,000 DXA 11,000 QUS installation reference

Scanning Methods Traditional X-rays cannot measure bone density. A number of different types of BMD tests are available, but the gold standard is DXA.

1) DXA (Dual-energy X-ray Absorptiometry) measures the spine, hip or total body

2) SXA (single-energy X-ray absorptiometry) measures the heel or wrist

3) DPA (dual photon absorptiometry) measures the spine, hip or total body

4) SPA (single photon absorptiometry) measures the wrist

5) QCT (Quantitative Computed Tomography) measures the spine or hip

6) PQCT (peripheral QCT) measures the forearm

7) QUS (Quantitative Ultrasound) uses sound waves to measure the heel or finger

WHO Gold standard

WHO defines DXA

as gold standard BMD technology with the most accuracy

What is DXA ?

DXA(Dual energy X-ray Absorptiometry) is a measurement technology based on the variable absorption of X-ray by the different body components and uses high and low energy X-ray photons.

1. X-ray beam penetrates both bone and soft tissue.

2. Low and High Energy attenuation coefficients and mass absorption coefficients for Bone & Soft

tissues are different.

3. Acquire photon counts before and after X-ray in each tissue. (Io, I).

4. Calculate the system of simultaneous equations by putting the 𝐼ℎ𝑜 and 𝐼𝑙𝑜 values into a common

denominator using the equations for the high energy 𝐼ℎ value and the low energy 𝐼𝑙 value.

5. It is possible to get the areal densities (g/cm^2) of the bone and soft-tissue, and by this value

we can calculate the mass and ratio.

Cone Beam DXA

pDXA(Peripheral Dual-energy

X-ray Absorptiometry)

Fast operation by

Cone Beam X-ray

Mono Tank

(Tube & Generator)

CCD camera detector

QUS

QUS(Quantitative Ultrasound

System)

Safe operation by

Ultrasound wave

SOS: Sound of Speed

BUA: Broadband

Ultrasound

Attenuation

Fan beam DXA

Fan beam DXA(Fan beam Dual-X ray

Absorptiometry)

Most efficient fan

beam technology to

cover large scan area

and high speed scan

(fan beam technology)

X-ray Point source

Detector

0.5 MHz

Ultrasonic transducer

Pencil beam source

Pencil beam DXA

Central DXA(Central Dual-energy

X-ray Absorptiometry)

Best precision bone

Densitometry as Gold

Standard which is

recommended by

WHO

Detector

Fan beam source

Detector array

BMD technology of Osteosys

iNSiGHT : Special Feature

DXA TECHONOLGY

1 NON-INVASIVE ANALYSIS

2 LONGITUDIANL IN-VIVO F/U

3BODY COMPOSITIN ANALYSIS FOR WHOE BODY AND EACH REGION OF INTEREST

4ACCURATE RESULTS FOR LEAN/FAT/BONE (<CV 1%, 𝑅2 > 0.99)

5 FAST SCAN( <25 sec)

6 QUICK&EASY PRE-TREATMENT

7NO RADIATION FOR RESEARCHER& MINUMUM DOSE FOR ANIMAL

DXA System Bone for Laboratory Animals- Mineral Density and Body Composition Analysis

FLAT PANEL DETECTOR

HIGH RESOLUTION (Pixel size of 100µ𝒎)

DR IMAGES FOR BONE/CARTILAGE, FAT, LEAN DISTRIBUTION ANALYSIS

WIDE SCAN AREA(16.5cmX25.5cm)

DXA FEATURES DESCRIPTION

NON-INVASIVE ANALYSISMaximize cost and labor savings through non-invasive analysis, rather than traditional chemical composition analysis, which was expensive and energy intensive.

LONGITUDIANL IN-VIVO F/U

Follow-up of body composition and bone density changes in the In-Vivo situation is possible without sacrifice of experimental animals.

ACCURATE RESULTS FOR LEAN/FAT/BONE

(<CV 1%, 𝑅2 > 0.99)

Measurement error within 1% (Bone; Precision Error & Accuracy Error in Static Condition). Precision: Compared to Chemical component analysis, 𝑅^2=0.99 or higher

FAST SCAN(<25 sec)

It is a Cone Beam type technology that captures a subject at a time; allows the shortest time among Lab DXA equipment unlike Fan Beam technology that scans a subject by “scratching”.

QUICK&EASY PRE-TREATMENT

No need to dissect experimental animals, only simple injection / breathing anesthesia; Maximize the time and labor savings of pretreatment.

NO RADIATION FOR RESEARCHER & MINUMUM

DOSE FOR ANIMAL

Full blockade of the researcher's radiation exposure by a cabinet-type full shield. Minimization of animal exposure dose compared to micro CT.

FLAT PANEL DETECTOR FEATURES

DESCRIPTION

HIGH RESOLUTION (Pixel size of 100µ𝒎)

100µ𝒎 a-Si TFT flat panel detector provides 16lp / mm high resolution image, better than 3.5lp / mm standard DR (4x magnification mode).

DR IMAGES FOR BONE/CARTILAGE, FAT, LEAN DISTRIBUTION

ANALYSIS

Through high resolution image, it is possible to track changes in bone, cartilage, fat distribution, and muscle on a daily, weekly and monthly basis after treatment of medication, exercise therapy, and functional food.

WIDE SCAN AREA(16.5cmX25.5cm) Wide scan area; Small animals up to 500g can be measured.

iNSiGHT : Software

Emergency switch

Shooting plate

Digital DetectorPlate

Radiation shielding window

Cone beam HFG

Power Switch

Scan Time 25sec.

Measurement Window for each ROI

Parameter UnitDescription

(FOR TOTAL BODY & EACH ROI)

BMC gBone Mineral Contents(Bone Mass);

= Density X Area

FAT g FAT Mass

FAT Ratio %Tota l Body Fat Rat io

=FAT/Tota l Mass

LEAN g Soft Tissue – Fat Mass

Total Mass gTota l Mass

=FAT+LEAN+BONE

BMD g/㎠ Bone Mineral Density

Bone Area ㎠ Bone Area of the Image

Tissue Area ㎠ Tissue area of the Image

Color Mapping for Fat/Lean Visualization

X-ray Image by iNSiGHT Bone-Enhanced Image

DR Image

Skull

Femur

History Analysis for Each ROI

Length ROI Setting- Measure only length

Analysis ROI setting function- Compatible with current SW

Color Visualizing Function (1)- Indicate specific parameter separately

Color Visualizing Function (2)- Overlapping with X-ray image (transparency adjustable)

Color Visualizing Function (3)- Adjustable color of each parameter

VET DXA iNSiGHT

iNSiGHT : Clinical Evidence

Objectives

We examined the precision, accuracy, and capability of detecting changes of Dual-Energy X-ray Absorptiometry(DXA) for the measurements of total-body weight(TBW), total-body fat weight(TBFW), and total-body lean weight(TBLW) in in an 8-week follow-up study of rats.

Materials and Methods20 male rats(4-week) were divided into 2 diet groups. For 8 weeks, we measured body composition(TBW, TBFW, TBLW) by DXA and TBW by an

electronic scale once a week. In week 8, we measured body composition 5 times by DXA and TBFW by dissecting experiment(EXP) of euthanized rats(12-week). Total-body fat

ratio(TBFR) was defined as TBFW / (TBFW+TBLW). The precision of DXA was evaluated by measuring the coefficient of variation(CV) and accuracy was evaluated by comparing DXA-derived data with EXP data.

The capability of detecting changes of DXA in follow-up study was verified by analyzing the trend of DXA-derived values over the 8 weeks.

ResultsFor TBW, TBFW, TBLW of DXA, CVs were 0.02±0.01, 0.10±0.05, 0.03±0.02 and errors were -6.996 ±3.429 (r=0.999), +14.729 ±3.663 (r=0.982), -21.725 ±4.223 (r=0.991). Prediction models were [EXP TBW = -31.767 +1.085(DXA

TBW), R2=0.998, root mean square error (RMSE)=1.842] and [EXP TBFR = -0.056 0.056 +1.177(DXA TBFR), R2=0.948, RMSE=0.007]. Over 8 weeks, DXA TBW and and DXA TBLW steadily increased, DXA TBFW steadily increased followed by saturation ordeclination, difference of DXA TBFW between 2 diet groups steadily increased.

Conclusions

Our study verified that DXA(iNSiGHT VET DXA, OsteoSys, Korea) is accurate and and precise enough to measure body composition of rats. Additionally, we confirmed the possibility that DXA could be used for the long-term follow-up studies.

VET DXA iNSiGHT

iNSiGHT : Comparative Devices

Micro CTDXAs for Animal NMR

Function iNSiGHT NMR Micro CT

3D Image N/A N/A YES

Slice Image N/A N/A YES

2D DR Image YES N/A YES

BMD(g/㎠) YES N/A

PARTLY YES(BY GRAY SCALE MAPPING, NOT BY DXA’S MATERIAL ANALAYSIS. LESS ACCUARATE THAN DXA)

BMC(g) YES N/A

YES(BY GRAY SCALE MAPPING, NOT BY DXA’S MATERIAL ANALAYSIS. LESS ACCUARATE THAN DXA)

FAT(g) YES YESOPTIONAL

(DEPENDS ON DEVICE)

LEAN(g) YES YESOPTIONAL

(DEPENDS ON DEVICE)

FAT(%) YES YES N/A

Bone Area(㎠) YES N/A N/A

Free Body Fluid(Water) N/A YES N/A

Heavy Animal(500g) Measurement

YES N/A N/A

Price LOW MIDDLE HIGH

Cost of Ownership LOW MIDDLE HIGH

Item Comment InAlyzer iNSiGHT VET DXA

Specifications

X-Ray System Equivalent DXA(Dual Energy X-ray Absorptiometry) DXA(Dual Energy X-ray Absorptiometry)

Scan Method INSIGHT Better (Faster Scanning) Fan Beam Cone Beam

Scan Site Equivalent Small Animal Total Body Small Animal Total Body

Scan TimeINSIGHT Better (X-ray Exposure

and Total Scan time)

(fast mode)x-ray time = 25s

scan time = 60s under

(common mode)x-ray time = 10s

scan time = 25s under

Measurment Parameter EquivalentBody Composition (Fat/ Lean/ BMC/ BM

D / FAT%)BMD, BMC, Bone/Tissue Area, Fat%, Fat(g), Lean(g), Total Weight @ each ROI

Precision Equivalent 1% (CV)<1% (CV) @phantom

<1% (CV) @total body weight of mouse, rat (short term,fixed position, n = 5)

AccuracyUndetermined (different unit

values provided)1% (CV)

>0.99 (R2) @phantom>0.99 (R2) @total body weight of mous

e, rat (n=20)

Positioning Equivalent Center preffered, in scan area lineCenter preffered, in scan area line of eac

h magnification level

Image areaInAlyzer Better

* Note: 2 different model existed210 mm X 315 mm, 140 mm X 210 mm 165mm x 255mm @1.2X

Pixel size INSIGHT Better 108 x 108 um 100µm @1.2X, 31µm @4X

Operating System Undetermined Windows 7/ 8 (32bit, 64bit) Windows 10 64bit (recommended)

Monitor Resoltution INSIGHT Better 1280 x 768 (1920 x 1080) 1920 x 1080

DimensionInAlyzer Better (Smaller the better)

* Note: Longer SID of iNSiGHTallows less distortion

740(W) x 430(D) x 717(H) 660(W) x 605(D) x 1130(H)

Weight InAlyzer Better (Lighter the better) 95kg 160Kg

Power/ Environment Equivalent 90 ~ 264VAC 110/240VAC, 50/60Hz, 200VA

Operating Temp Equivalent 10 ~ 35 ℃20 ~ 25 ℃ (recommended), 10 ~ 35 ℃ (

maximum)

Features

Size of AnimalInAlyzer Better

* Note: Officially, maximum size is rat (Mainly Mouse)

Small animal such as mouse(10~50g) or Gerbil, Middel size such as Rabbit,

Guinea Pig, Dog, Cat

Small animals less than 500g (Upcoming upgrade)

The number of Body Composition ROI

INSIGHT Better Maximum 5 Manual ROIs Unlimited Manual ROI

Efficiency of Analyze INSIGHT Better

X-ray irradiation time less than 30 seconds in one measurement,

measurement result can be checked within 60 seconds (Optimum mode

180sec, Accuracy mode 300sec)

X-ray irradiation time less than 10 seconds in one measurement, measurement result can be checked within 30 seconds (Excluding ROI setting time)

Precision Equivalent Less than 1% CVLess than 1% CV

(for Phantom and fixed animal)

Radiation Shielding Undetermined (No detailed info) Raditation Shielding (No detailed info)below 10mRem per examination (within

5m)Real-time Measurement

StatusUndetermined (Pros & Cons for

each product)Built-in Camera lead glass window (upcoming upgrade)

Back-up EquivalentData and Image can be saved as Excel

and Tiff formatExtract result data (csv format),

view image (bmp format)

Resoultion of Image

INSIGHT Better* Note: Magnification available,

HQ DR applied

54um linear detector; 5.0lp/mm (Better than 3.5lp/mm DR)

*Note: Error in the specification - sensor resolution [lp/mm] = 1000 / (2 * pixel

size [um])

Provides a high-resolution image of 5.0 lp/mm (@ x1.2 magnification), 16.0 lp/m

m (@ 4X magnification)

Item Comment InAlyzer iNSiGHT VET DXA

VET DXA New Gold Standard

FAST Scan 25sec.

DXA Original

Technology

DR Image

Customized Feedback

Accuracy : R2 >0.9Precision : CV<1%

Simple Operation