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AAPM 54th Annual Meeting Charlotte, North Carolina

August 2, 2012

Mats DanielssonRoyal Institute of Technology (KTH) Stockholm,Sweden

md@mi.physics.kth.se

Philips Microdose Mammography-the Technology and Physics Behind the First FDA Approved Photon Counting X-ray Imaging System

Physics of Medical Imaging at the Royal Institute of Technology in Stockholm

Disclosure Statement

Founder of Sectra Mamea AB which was acquired by Philips.

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Challenges in Mammography Today

•10-40% of cancers missed

•Recall rate 1%-20%

•Cost

•Radiation Dose

•Dense breasts !

What may help us?

-Get rid of superimposed tissue

-Visualize blood vessels associated to the cancer with contrast agent

-Visualize the cancer with dual energy (spectral imaging)

-More efficient sensors

Fundamental Problem:Fundamental problem:

”Convert an x-ray photon into electric charge which you measure”

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Who counted photons first?

What was that?

Maybe a photon

X-ray photon

To Count Photons – No Electronic Noise

Energy

Threshold 3

1 2 3Noise Time

Threshold 2

Threshold 1

Integrating Current:Today’s praxis in X-ray Imaging

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X-ray photons

Energy

Time

4

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•••• Comparison of FFDM Technologies

aSi flat panelX-ray Photon

Scintillator amplification

Light

Capacitor charge storage

Analog signal

A/D - Converter

Digital signal

aSe flat panelX-ray Photon

aSeX-ray into electrons

Electrons

Capacitor charge storage

Analog signal

A/D - Converter

Digital signal

Photon CountingX-ray Photon

MicroDose Detector

Digital signal

5 (00000000000101)

Analog Analog

What is difficult with photon counting?

Measured Effect of Dead Time

E. Fredenberg et al. SPIE 7258 (2009)

R.L. Lucke Rev. Sci. Instrum. 47 (6):766 (1976)

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Measured Effect of Dead Time

E. Fredenberg et al. SPIE Physics of Medical Imaging 2009

Deadtime per event

189 ns

Deadtime at 20 kHz

0.4%

Deadtime at 200 kHz

3.7%

Philips – Photon Counting Mammography Today

Crystalline Silicon Detector

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Crystalline Silicon for Photon Counting

Spatial resolution Spatial Resolution in Mammography

100 µm Image50 µm MicroDose Image

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Calcifications Case CC Close ups (from study by Cole et al.)

FFDM Microdose

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“Diagnostic Scan” is Microdose alternative to Geometric Magnification

Use high DQE and deploy higher dose on the spot compression area. No magnification table.

• Phantom evaluation shows Diagnostic Scan achieves better image results at a lower dose compared to Geometric Magnification.

• “Performs comparably or better than conventional geometric magnification for the detection of masses and micro-calcifications, with the exception of mass lesions in larger breast, where GE conventional geometric magnification yields superior results” according to Egan et al, IWDM Philadelphia, PA (2012)

CONFIDENTIAL

Photon Counting

Virtually Eliminates all Scatter Radiation

Conventional Photon Counting

Scatter No Scatter

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Scattered radiation

Monnin et al. Med. Phys., vol. 34 (3), pp. 906-914, 2007

DQE at Zero Spatial Frequency

DQ

E(0

)

PHILIPS MicroDosePhoton Counting

System DQE

Åslund, M. et al., 2010. Detectors for the future of x-ray imaging. Radiation

Protection Dosimetry, 139(1-3), pp. 327-333

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Does the clinical performance match the physics?

Example 1:Experience from BreastCheck, The Irish Breast Screening Program

• 4 static & 16 mobile screening units

• Equipment:– 11 CsI scintillator– 10 a-Se– 7 Photon counting

The British Institute of Radiology, doi: 10.1259/bjr/29747759

Ireland Breast Screening Program Cancer Detection Rates

Mccullagh et al. The British Institute of Radiology (2011), doi: 10.1259/bjr/29747759

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The British Institute of Radiology, doi: 10.1259/bjr/29747759

Ireland Breast Screening Program Cancer Detection Rates

Mccullagh et al. The British Institute of Radiology (2011), doi: 10.1259/bjr/29747759

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

mG

y

Average Mean Glandular Dose

Philips MicroDose*

GE Essential

Hologic Selenia

P Baldelli et. al., “Comprehensive Dose Survey Of Breast Screening In Ireland”, Radiation Protection Dosimetry , Vol. 145, No. 1, pp. 52–60, 2010

Ireland Breast Screening Program Radiation Dose

E Cole, A Toledano, M Lundqvist, E Pisano

"Comparison of Radiologist Performance with Photon-Counting Full-Field Digital Mammography to Conventional Full-Field Digital Mammography”

Academic Radiology, Vol 19,(8) p 916-922, August 2012

Example 2:

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Microdose versus standard FFDM

• Multi-slit Scanning Full-Field Digital Mammography System with Photon Counting Detector (Philips Mammography L30)

• Comparison Study between Philips L30 and GE FFDM conducted in 2010– Multi-Case, Multi-Reader Study– Feature Analysis Study– Assessment of Dose Differences based on Breast Density, Breast

Thickness

Microdose versus standard FFDM

• 16 MQSA qualified Radiologist Readers• 133 women (≥ age 40) from two European Sites: one in United

Kingdom and one in Switzerland– 67 women were in the Normal Cohort (underwent Philips Microdose

Mammography as part of their routine screening exam after having had a GE FFDM screening mammogram 10-30 months prior) [67 normal].

– 66 women were in the Diagnostic Cohort (had a screening Philips MDM mammogram and underwent diagnostic imaging with GE FFDM) [17 biopsy benign, 49 cancer]

• Review Workstations at ACR Image Metrix Facility in Philadelphia, PA

• Each reader reviewed all 133 cases at two separate visits at least one month apart. Modalities were counterbalanced.

• Readers evaluated the images for presence of suspicious findings providing a BIRADS score(1-5) and a Probability of Malignancy score 0-100

Microdose versus standard FFDM

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Microdose versus Standard FFDM

Philips L30 GE FFDM Difference p-value

AUC 0.947 (0.920, 0.974)

0.931 (0.898, 0.964)

0.016 (-0.001, 0.034)

<0.001

Sensitivity 0.936 (0.897, 0.976)

0.908 (0.856, 0.960)

0.028 (-0.003, 0.059)

<0.001

Specificity 0.764 (0.688, 0.841)

0.749 (0.668, 0.830)

0.015 (-0.022, 0.052)

<0.001

Feature analysis resulted in Microdose being preferred to standard FFDM by the readers for >70% of the cases

The average mean glandular dose for Microdose was 0.74 mGy

FFDM average mean glandular dose was 1.23 mGy

Evidence from clinical trials:B. Hedson et al, "Digital vs. Screen-Film Mammography: A retrospective Comparison in a Population-Based ScreeningProgram”, European Journal of Radiology, Volume 64, Issue 3, p 419-425

S Weigel , R Girnus , J Czwoydzinski , T Decker , S Spital , W Heindel “Digital mammography screening: average glandular dose and first performance parameters.Rofo. 2007 Sep ;179 (9): p 892-895

M.G. Wallis, “Evaluation and Clinical assessment of Digital Mammography Screening using a Sectra Microdose full field Digital X-ray unit”, NHSBSP Equipment Report 0601, NHS Cancer Screening Programmes 2006

E

Further clinical trials

Silicon is Proven Material

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Transport & storage not a problem

temperatures from -10 C to 50 C

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-You need to be ready for the next photon, no “recovery time” for detector between exposure.

-Curved surface and warm patient support = patient comfort

Also…

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Philips MicroDose status summary

-Low dose and high image quality

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But what will happen in the future?

3

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Challenges in Mammography Today

•10-40% of cancers missed

•Recall rate 1%-20%

•Cost

•Radiation Dose

•Dense breasts !

What may help us?

-Get rid of superimposed tissue

-Visualize blood vessels associated to the cancer with contrast agent

-Visualize the cancer with dual energy (spectral imaging)

-More efficient sensors

HighReX - a European Union Project

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HighReX

Objectives

•Develop novel imaging methods using– 3D– dual energy– contrast mammography

•with improved detection and diagnosis of breast cancer compared to current technology

Multi-center clinical trial

Finalized 2010

Duration: 3.5 years

HighReX projectCoordinator, (M. Danielsson)system supplier• Sectra Mamea AB, Sweden (aquired by Philips Sep. 2011)Clinical Partners• Addenbrooke’s Hospital, Cambridge, UK (M. G. Wallis)• S:t Göran’s Hospital, Stockholm, Sweden (K. Leifland)• Charité Hospital, Berlin, Germany (F. Diekmann)• Münster University Hospital, Munster, Germany (W. Heindel)• Health Unit of Pistoia, Florence, Italy (M. Rosselli del Turco)• Arcades, Marseille, France (B. Seradour)Other partners• Royal Surrey County Hospital NHS Trust• Stichting Landelijk Referentie Centrum voor Bevolkingsonderzoek• Radboud University Nijmegen Medical Centre

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Photon Counting Tomosynthesis

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Geometry

Reconstructed volume

Projections

Geometry

Photon Counting Tomosynthesis

• Scanning multi-slit system– Virtually no scatter radiation– Short exposure time (~1 s)

• Photon counting detector– Intrinsically fast image read-out– Lower x-ray dose without compromising image quality– No electronic noise (especially important in tomo)– High resolution 50 micron pixel

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Technical Data

• X-ray tube and detector move in a synchronized motion

• Tomosynthesis angle: 11 degrees• Scan angle of x-ray tube: +/- 17 degrees• Exposure time for a point << total scan time (~1

second exposure time)• Projections: 21 – one per detector line• Dose level from current clinical trial, prototype: 0.8

mGy for average breast,

Tomo2D

HighReX Cases

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Spiculated mass

2D Tomo

Cyst

Tomo2D

Spiculated mass

Tomo2D

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Tomosynthesis Clinical Results

• Photon counting tomo vs FFDM• 10+10 readers, 130 cases (40 cancers, 24 benign, 66 normals)• Results published in Radiology 2012 (1): Two-view

tomosynthesis outperforms FFDM for less experienced radiologists (< 10 yrs) when measured as AUC scores for diagnostic accuracy, and also when measured by lesion type for masses and calcifications separately.

• No significant differences for one-view tomosynthesis vs FFDM• Photon counting tomo dose was only 0.7-0.82 mGy

(1) Two-View and Single-View Tomosynthesis versus Full-Field Digital Mammography: High-Resolution X-Ray Imaging Observer Study Radiology March 2012 262:3 788-796; Published online January 24, 2012, doi:10.1148/radiol.11103514

From: Marian Strassner [mailto:mstrassner@rsna.org] Sent: 17 May 2012 22:38To: Wallis, MatthewSubject: Your article in Top 10 Most Read Dear Dr Wallis, We are pleased to inform you that your article Matthew G. Wallis, Elin Moa, Federica Zanca, Karin Leifland, Mats DanielssonTwo-View and Single-View Tomosynthesis versus Full-Field Digital Mammography: High-Resolution X-Ray Imaging Observer StudyRadiology Mar 01, 2012 262: 788-796. has been listed as one of the ‘Top 10 Most Read Recent Articles’ in Radiology for the last 3 months (February-

April 2012).

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Contrast Agent

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• Clinical trialso 2010o Charité University

Hospital Berlino Dr. Felix Diekmanno Iodine Enhancement

• 35 mm invasive lobular carcinoma

• Difficult to detect in 2D• Difficult to detect in

tomosynthesis• Energy subtraction –

clear improvement in this case

Courtesy Dr. Felix Diekmann

HighReX

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Spectral Imaging

Photons

Energy

Threshold 1

1 2 3Noise Time

Single-shot spectral mammography

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21

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Single-shot spectral mammography

Energy

Threshold 1

1 1 2Noise Time

High-energy Photons

Threshold 2

Low-energy Photon

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CONFIDENTIAL

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On the photo you can tell what is what…

Acrylic

Aluminum

Aluminum

Acrylic

Acrylic

CONFIDENTIAL

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But on the X-ray image, can you tell what is what?

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Spectral image of acrylicSpectral image of Aluminium

On photon counting spectral you can!

All acrylic removed Aluminum removed

AlAl

Single-shot spectral imaging

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2) Lesion evaluation*

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1) Breast density measurements *

Providing the radiologist with objective data to help assess suspicious lesions

Providing the radiologist with objective data to assess individual risks

Applications for single-shot spectral mammography in screening

And much more to come…

Information acquired with theregular mammogram

- no extra views - no extra acquisition time- no extra radiation- no contrast injection

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fatty dense

Breast cancer risk

Mammography sensitivity

Spectral imaging - breast density measurementsWhy?

Spectral imaging - breast density measurementsHow does it work?

DICOM structured reportDICOM header data

Glandularity: 16%BIRADS code: 1

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Spectral imaging - breast density measurementsWhat are the benefits?

• Objective data to assess and classify breast density

• Enables personalized care- Choice of modality- Screening interval- Reader focus and efforts

fatty dense

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Spectral imaging - lesion evaluationWhy?

• Recalls for benign findings are a major problem in screening

– Increased costs – The cost of diagnostic workup and assessment of a recall is approximately eight times the cost of the screening

– Unnecessary stress and exam for women

• Up to 20% of recalls are due to circular lesions which are easy to detect but difficult to characterize

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Spectral imaging - lesion evaluationHow does it work?

Lesion content: WaterLesion diameter: 13 mmLesion thickness: 6 mmBreast thickness: 39 mmROI glandularity: 28%

Spectral imaging - lesion evaluationWhat are the benefits?

• For the radiologists– Objective data to evaluate lesions water content– Reduced costs generated by unnecessary recalls

• For the woman- Possibility to avoid uneccessary exams and stress- Low dose

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Publications• SPIE 2009

– A photon-counting detector for dual-energy breast tomosynthesis, E. Fredenberg, M. Lundqvist, M. Aslund, M. Hemmendorff, B. Cederstrom, M. Danielsson

The photon-counting detector enables dual-energy subtraction imaging with electronic spectrum splitting. This improved the detectability of iodine in phantom measurements, and the detector was found to be stable over typical clinical acquisition times.

• SPIE 2010

– Observer model optimization of a spectral mammography system, E. Fredenberg, M. Lundqvist, M. Aslund, B. Cederstrom, M. Danielsson

• SPIE 2011

Evaluation of photon-counting spectral breast tomosynthesis, N. Dahlmana, E. Fredenberga, M. Åslund, M. Lundqvist, F. Diekmann, M. Danielsson

It was shown experimentally that unenhanced spectral imaging may increase detectability of tumors in the order of a factor two if anatomical noise dominates. The model comparison revealed that contrast-enhanced spectral imaging and tomosynthesis can be combined to

improve tumor detectability.

– Optimization of mammography with respect to anatomical noise, E. Fredenberg, B. Svensson,M. Danielsson, B. Lazzari, B. Cederstrom

Publications

• Other

– Contrast-enhanced spectral mammography with a photon-counting detector, E. Fredenberg, M. Aslund, M. Hemmendorff, B. Cederstrom, M. Danielsson, Med. Phys. (2010) Vol. 37, No. 5, May

– Energy resolution of a photon-counting silicon strip detector, E. Fredenberg, M. Aslund, M. Lundqvist, B. Cederstrom, M. Danielsson, Nucl. Instr. and Meth. (2010) Vol. 613, No. 1, pp. 156-162

– Detectors for the future of X-ray imaging, E. Fredenberg, M. Aslund, M. Telman, M. Danielsson, Radiation Protection Dosimetry (2010), Vol. 139, No. 1–3, pp. 327–333

• SPIE 2012

– Lesion characterization using spectral mammography, E. Fredneberg PhD, K. Leifland MD, B. Norell PhD, B. Cederström PhD, M. Lundqvist PhD

– Photon-Counting Spectral Phase-Contrast Mammography, E. Fredenberg, E. Roessl, T. Koehler, U. van Stevendaal, I. Schulze-Wenck, N. Wieberneit, M. Stampanoni, Z. Wang, R. A. Kubik-Huch, N. Hauser, M. Lundqvist, M. Danielsson, M. Åslund

– Prof. Dr. Walter Heindel, Referenzzentrum Mammographie, Am Universitätsklinikum Münster, Münster, Germany

Does it help?

• Contrast agent-Yes (but not in screening)

• Spectral Imaging-Maybe

• Tomosynthesis-No

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Quality Control and Physics Measurements

• Based primarily on– IEC standards (e.g. IEC 61223-2-10, IEC 61223-3-

2)– European guidelines for quality assurance in breast

cancer screening and diagnosis, 4th Ed. (European Comission)

– MQSA– Our own experience and knowledge about critical

system parameters

Philips Micodose QC philosophy

Overview of Some Medical Physicist QC Tests

For detailed step-by-step procedures for all tests please see the QC manual or contact David Nelson David.Nelson@philips.com

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Structure of QC procedures

Frequency Performed by

Daily

QC technologistWeekly

Monthly

Quarterly

Annual Medical physicist

Medical Physicist QC procedures –Annual

Annual

1 X-ray tube output

2 Air kerma reproducibility

3 Half value layer (HVL)

4 AEC: Breast thickness tracking

5 AEC: Density compensation

6 Image quality evaluation

7 CNR reference level

8 Tube voltage

9 Image field and x-ray field agreement

10 Missed tissue at chest wall

11 Viewing conditions

12 Guidance system control

MicroDose Differences

-Good to know for the physicist

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Spatial resolution?

Different blurring mechanisms in the two directions

Spatial resolution, cont.

• Slit-direction:

– Similar to other systems:resolution best on patient support in the MicroDose

• Scan-direction:

– Opposite to other systems:resolution best farthest up in the MicroDose

MTF at two heights

0 2 4 6 8 10 12 14 16 18 200

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1MTF 6 cm from chest wall and on pat. supp.

Spat. freq. [lp/mm]

MTF

[r.u

.]

Slit dir.Scan dir.

0 2 4 6 8 10 12 14 16 18 200

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1MTF 6 cm from chest wall and 5 cm above pat. supp.

Spat. freq. [lp/mm]

MTF

[r.u

.]

Slit dir.Scan dir.

On breast support 5 cm above

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Spatial resolution, cont.

• Slit-direction: MTF factors

– Focal spot length– Pixel size

• Scan-direction: MTF factors

– Focal spot width– Collimator slit width

Recommended test

• Monthly QC test using line pair phantom placed on top of BR12 or acrylic plate (~45 mm)

• Both parallel and perpendicular to scan direction• Only technologist needs to perform this test• Pass criteria is visibility >= 6 lp/mm• We would like the physicist to be aware of the test

MicroDose – mAs

By mAs we mean effective mAs

• Conv. mAs = tube current × exposure time

• Eff. mAs = tube current ×(eff. exposure time for one point in image)

• Eff. mAs = conv. mAs ×open width in collimator/ total scan length

• Eff. mAs ≈ conv. mAs × 1%• If not explicitly stated otherwise we

always mean eff. mAs

Detector lines

Scan direction

Multi-slit collimator

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MicroDose – mAs

By mAs we mean effective mAs

• Conv. mAs = tube current × exp. time• Eff. mAs = tube current ×(eff. exposure time for one point in image)

= conv. mAs × open width in collimator / total scan length≈ conv. mAs × 1%

Pulse duration = 10- 50 msecPulse freq = 5-30 per sec

Required Tools for Medical Phycisist QC

Medical Physicist Required Tools

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Medical Physicist Required Tools (contd.)

Unfors jig for dose measurements

• Radiation to detector is pulsed (ensure your dose meter can handle it)• W/Al anode/filter combination (meter calibrated for e.g. Mo/Mo can

give very wrong results)• Scale dose using inverse square law to 45 mm above patient

support. Source-to-patient support = 640 mm

• Measured values should be within

+/-20% of system calculated• Air Kerma reproducability

must be within 5% rel. stdev

Tube Output Measurements Considerations

HVL

• Use ion chamber or other dose meter calibrated* for the radiation quality of the MicroDose system (W anode and 0.5mm Al filtration).

• Place compression paddle 9 cm above patient support to minimize scatter effects.

• Place a lead sheet with hole on paddle.• Verify collimator is lined up with dose

meter.• Place Al filters on lead sheet as required.

* Ion chambers work fineSolid state detectors

- Unfors is calibrated- In discussions with RadCal and Keithly

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Exposure and CNR Test

• Verifies AEC ensuring optimal exposure• Acrylic is not equivalent to breast tissue• Flat acrylic on curved surface introduces bias• System corrects for thickness measurement• Test uses acrylic plates 20-70 mm

and 0.1/0.2 mm Al filter• Use ROI tool to calculate CNR• Use HVL and air kerma to calculate AGD

- use breast thickness not acrylic thickness• AGD = ESAK x g x c x s (QC manual)

• Measured AGD shall be within ±15% of system value• CNR should exceed CNR threshold (QC manual) ~13 mm

gap

Phantom Image Quality

• Acquire ACR phantom image (no disk)• Score the phantom on AWS or RWS• At least 4 fibers, 3 groups of micro-calcifications, and 3 masses

must be seen (total score must be at least 10)• Calculate dose and should not exceed 1 mGy

CNR Reference Level

• Establish operating level of CNR• Phantom available from Philips• Use Daily Quality Control (DQC) tool• Measure CNR and establish reference value• QC Tech to ensure daily CNR is within +/-10% of reference

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SNR Test

• To check if constant SNR is maintained regardless of breast transmission• Acrylic slabs 30-50 mm in 5 mm steps• Use ROI tool• SNR calculated for each slab thickness• Measured SNRs to be within +/- 15% of average SNR value

Summary

-Important to know some tricks of the trade for QC

-No scattered radiation and photon counting result in high image quality at half the radiation dose

-Future possibilities with spectral imaging

Thank’s!