Molecular Breast ImagingMolecular Breast ImagingMolecular Breast Imaging Molecular Breast Imaging New Modality for New Modality for Di i B t CDi i B t CDiagnosing Breast CancerDiagnosing Breast Cancer

By Lillian H. Stern, M.D.By Lillian H. Stern, M.D.

Don’t we have Don’t we have enoughenough tools tools f di i B tf di i B tfor diagnosing Breast for diagnosing Breast Cancer???Cancer???

Current ModalitiesCurrent ModalitiesCurrent ModalitiesCurrent Modalities

Mammograms (analogue Mammograms (analogue vv. digital). digital) TomosynthesisTomosynthesis TomosynthesisTomosynthesis UltrasoundUltrasound

MRIMRI MRIMRI PET ScanPET Scan Molecular Breast Imaging (BSGI. MBI, Molecular Breast Imaging (BSGI. MBI,

PEM)PEM)))

Why do we need another Why do we need another yytool?tool? Many articles state that we miss Many articles state that we miss 10%10%

of breast cancer on mammography.of breast cancer on mammography.g p yg p y It really is much higher especially in It really is much higher especially in

dense breasts!dense breasts!------It may be as high asIt may be as high asdense breasts!dense breasts! It may be as high as It may be as high as 30%30%..

Dense tissue camouflages cancersDense tissue camouflages cancers Dense tissue camouflages cancers Dense tissue camouflages cancers until they enlarge, become brighter until they enlarge, become brighter than the surrounding tissue or formthan the surrounding tissue or formthan the surrounding tissue, or form than the surrounding tissue, or form discrete margins and/or calcifications. discrete margins and/or calcifications.

Old and new tools for Old and new tools for detecting breast cancer.detecting breast cancer. Mammography is still the “Mammography is still the “GoldGold

StandardStandard.”.”

Digital MammogramsDigital MammogramsDigital MammogramsDigital Mammograms

Performed just like a regular Performed just like a regular mammogram.mammogram.gg

Still need compression.Still need compression. Image is just recorded differentlyImage is just recorded differently Image is just recorded differentlyImage is just recorded differently--------

on a computer instead of xon a computer instead of x--ray film.ray film.C th d ti b ttC th d ti b tt Can see thru dense tissue better.Can see thru dense tissue better.

DigitalDigital AnalogueAnalogueDigitalDigital AnalogueAnalogue

Solid Mass withSolid Mass withCalcificationsCalcifications

TomosynthesisTomosynthesisTomosynthesisTomosynthesis

33--Dimensional picture using FFDM.Dimensional picture using FFDM. Multiple XMultiple X--ray pictures of the breastray pictures of the breast Multiple XMultiple X ray pictures of the breast ray pictures of the breast

from many angles.from many angles. Clears overlapping densities hiding anClears overlapping densities hiding an Clears overlapping densities hiding an Clears overlapping densities hiding an

underlying abnormality.underlying abnormality.

3D Mammography 3D Mammography (Tomosynthesis)(Tomosynthesis)

•• Step, expose Step, expose imageimage

(Tomosynthesis)(Tomosynthesis)

11 images, 5 11 images, 5 degrees degrees ggbetween between imagesimages

Total dose Total dose equal to single equal to single mammomammo

Total imaging Total imaging time about 7time about 7time about 7 time about 7 secondsseconds

Breast TomosynthesisBreast TomosynthesisBreast TomosynthesisBreast Tomosynthesis

It is hard to interpret thisWhen everything is overlappingI l i !!!It is hard to interpret thisWhen everything is overlappingIs overlapping !!!

Courtesy of Dan Kopans, M.D.

Breast TomosynthesisBreast TomosynthesisBreast TomosynthesisBreast Tomosynthesis

It is hard to interpret thisWh thiIt is hard to interpret thisWhen everythingIs overlapping !!!

Examples of Examples of ppTomosynthesisTomosynthesis

Tomosynthesis Mammography Tomosynthesis Mammography ReconstructionReconstruction

MRIMRI (Angiogenesis)(Angiogenesis)MRIMRI (Angiogenesis)(Angiogenesis) MRI is an excellent tool!MRI is an excellent tool!MRI is an excellent tool!MRI is an excellent tool!

When it is very positiveWhen it is very positive--it is dramatic.it is dramatic. But frequently it has severalBut frequently it has several But frequently it has several But frequently it has several

questionable areas which require a 6 questionable areas which require a 6 month followmonth follow--up or a repeat study at aup or a repeat study at amonth followmonth follow up or a repeat study at a up or a repeat study at a different time in the menstrual cycle. different time in the menstrual cycle.

Sometimes when patient comes forSometimes when patient comes for Sometimes when patient comes for Sometimes when patient comes for MRI biopsy, abnormal area no longer MRI biopsy, abnormal area no longer visiblevisiblevisible.visible.

MRI is expensive!MRI is expensive!MRI is expensive!MRI is expensive!

Some patients can’t have test because Some patients can’t have test because of of metal or pacemakers.metal or pacemakers.pp

Some patients Some patients can’t lay on stomachcan’t lay on stomach.. Some patients areSome patients are claustrophobicclaustrophobic Some patients are Some patients are claustrophobic.claustrophobic.

Radiologist has to scroll Radiologist has to scroll ggthru 700 images!thru 700 images! Patient usually has to wait several Patient usually has to wait several

weeks to get on the MRI schedule and weeks to get on the MRI schedule and ggmay have to come back for the may have to come back for the opposite breast.opposite breast.pppp

Patient may not get the results for Patient may not get the results for several daysseveral daysseveral days.several days.

MRI usually requires MRI usually requires precertification.precertification.

Anxiety!!!!Anxiety!!!!Anxiety!!!!Anxiety!!!!

Patient!!!Patient!!! Clinicians!!Clinicians!! Radiologists! Radiologists! Will I Will I

miss a cancer? Will miss a cancer? Will I be sued?I be sued?

Goals for decreasing Goals for decreasing ggeveryone’s everyone’s anxiety!anxiety! Decrease number of Decrease number of indeterminateindeterminate

StudiesStudies Decrease number of Decrease number of BIRADS 3 = 6 BIRADS 3 = 6

month followmonth follow--upupmonth followmonth follow up.up. Decrease number of Decrease number of benignbenign biopsies. biopsies.

Molecular ImagingMolecular ImagingMolecular ImagingMolecular Imaging

Instead of looking at structures Instead of looking at structures (anatomy) or angiogenesis, these tests (anatomy) or angiogenesis, these tests ( y) g g ,( y) g g ,analyze analyze cellular activitycellular activity..

Cancer cells are more active thanCancer cells are more active than Cancer cells are more active than Cancer cells are more active than normal cells and the mitochondria will normal cells and the mitochondria will therefore absorb more of the injectedtherefore absorb more of the injectedtherefore absorb more of the injected therefore absorb more of the injected radioactive isotope.radioactive isotope.

Molecular Breast Imaging Molecular Breast Imaging g gg gPositive Cancer on RightPositive Cancer on Right

Molecular Breast ImagingMolecular Breast ImagingMolecular Breast ImagingMolecular Breast Imaging

Involves an injection into a vein of a Involves an injection into a vein of a tracer dose of radioactive material.tracer dose of radioactive material.

Images of only the breast are obtained Images of only the breast are obtained using the same views as ausing the same views as ausing the same views as a using the same views as a mammogram. Direct comparison with mammogram. Direct comparison with the mammogram is therefore possible!the mammogram is therefore possible!the mammogram is therefore possible!the mammogram is therefore possible!

Active cells produce a black spot Active cells produce a black spot similar to a PET scansimilar to a PET scansimilar to a PET scan. similar to a PET scan.

BSGIBSGI ((DilonDilon) or ) or MBIMBI (Mayo (Mayo (( )) ( y( yClinic) Tc99 Clinic) Tc99 SestamibiSestamibi

Readily available (Can borrow a dose Readily available (Can borrow a dose from cardiac stress test.)from cardiac stress test.)))

Can quickly add on a patient already in Can quickly add on a patient already in departmentdepartmentdepartment.department.

No fasting. No delay after injection.No fasting. No delay after injection.N t i di tiN t i di ti No contraindications No contraindications

Isotope for PEM (Positron Isotope for PEM (Positron p (p (Emission Mammography)Emission Mammography) Use FDG similar to a PET scan.Use FDG similar to a PET scan. Patients must fastPatients must fast Patients must fast.Patients must fast. One hour delay between injection and One hour delay between injection and

imagingimagingimaging.imaging. Concern in DiabeticsConcern in Diabetics

ScintimammographyScintimammographyScintimammographyScintimammography

This is the old nameThis is the old name——developed in the developed in the 1990’s1990’s

Failed to demonstrate small cancersFailed to demonstrate small cancers

ScintimammographyScintimammographyScintimammographyScintimammography

Patient laid prone on a regular nuclear Patient laid prone on a regular nuclear medicine table.medicine table.

Detail was not good enough to pick up Detail was not good enough to pick up small cancerssmall cancerssmall cancerssmall cancers

The weakness of conventionalfbreast scintigraphy is the

low resolution of thed d

LFOV gamma camera - not ideal for breast imaging

standard gamma camera

SFOV gamma camera - anatomically specific

Th Dil 6800The Dilon 6800 Gamma Camera

The Dilon 6800 Gamma Camera can replicate any mammographic viewreplicate any mammographic view.

Oblique

Cranial Caudal MedialMedial

Comparative Resolution Based on Comparative Resolution Based on ppGeometric FactorsGeometric Factors

Distance = 0mmDistance = 50 to 90mm

Resolutionassuming 8CmResolution 6.0mm 10.0+mm 3 5mm 7 0mm

Distance 50mm 130mm 0.0mm 80mmassuming 8Cmcross section

of breast tissue

3.5mm 7.0mm

Dedicated cameras improve imaging by providing both better improved detector spatial resolution and by moving the targetspatial resolution and by moving the target closer to the detector

Partial Volume effectPartial Volume effect

100 100

Example A Example B

Detector

DetectorImage DetectorImage

Area of illumination = 1

The area of the object in both cameras contains the same number of

Area of illumination = 1so 100/1 = 100 object intensity = 100 Area of illumination = 2

so 100/2 = 100 object intensity = 50

counts so the counts/area of example A is higher than example B.This results in better contrast for the image in example B.

Impact of Attenuation

Contrast =0.34

Contrast = 0.40

Contrast = 0.47

Contrast = 0.54

Contrast = 0 63

Contrast = 0.86

Contrast = 0.74

Contrast = 0.63

Lesion Depth % of photons Contrast 0 100 1.0

Contrast = 1.0

1 85.8 0.86 2 73.6 0.74 3 63.1 0.63 4 54.2 0.54 5 46.5 0.47 6 49 9 0 56 49.9 0.5 7 34.2 0.34 8 29.3 0.29

What does all this mean?What does all this mean?What does all this mean?What does all this mean?The dedicated breast gamma camera The dedicated breast gamma camera designs greatly improve the sensitivity fordesigns greatly improve the sensitivity fordesigns greatly improve the sensitivity for designs greatly improve the sensitivity for small lesions through a combination of:small lesions through a combination of:

i d t i i ti l l tii d t i i ti l l ti–– improved extrinsic spatial resolutionimproved extrinsic spatial resolution–– Imaging the breast directly against the Imaging the breast directly against the

detectordetectordetectordetector–– Applying mild compressionApplying mild compression

The Clinical EvidenceThe Clinical Evidence

Over 10mm

6 - 10mm CZT DualCZT SingleDilon 6800

Under 5mm

0 20 40 60 80 100

Brem R, Floerke A, Rapelyea J, Teal C, Kelly T, Mathur V. Breast Specific Gamma Imaging as an Adjunct Imaging Modality for the Diagnosis of Breast Cancer Radiology 2008; 247(3):651 57Diagnosis of Breast Cancer. Radiology. 2008; 247(3):651-57.Hruska C, Phillips SW Whaley DH, Rhodes DJ, O’Connor MK. Molecular Breast Imaging: Use of a Dual-Head Dedicated Gamma Camera to Detect Small Breast Tumors. AJR:191, December 2008

Tc99mTc99m--Sestamibi HistorySestamibi Historyyy

Originally developed as a cardiac imaging agent Originally developed as a cardiac imaging agent -- FDA approved in 1991FDA approved in 1991-- Same day imaging limited to 40 mCi for stress and restSame day imaging limited to 40 mCi for stress and rest-- Two day imaging limited to 60 mCi for stress and restTwo day imaging limited to 60 mCi for stress and rest

Breast imaging was added to the drug data sheet in 1996Breast imaging was added to the drug data sheet in 1996-- Based on imaging conducted with standard gamma cameras, the Based on imaging conducted with standard gamma cameras, the

d d d 20 d d d 20 30 Ci30 Cirecommended dose was 20 recommended dose was 20 –– 30 mCi.30 mCi.-- The SNM adopted this recommendation in their Breast Scintigraphy protocolThe SNM adopted this recommendation in their Breast Scintigraphy protocol-- All of the studies published since then have utilized a 20 All of the studies published since then have utilized a 20 –– 30 mCi30 mCio e s ud es pub s ed s ce e a e u ed a 0o e s ud es pub s ed s ce e a e u ed a 0 30 C30 C

www.cardoilite.comwww.cardoilite.comwww snm orgwww snm orgwww.snm.orgwww.snm.org

BSGI Radiation BSGI Radiation DosimetryDosimetryyy

According to the National Institutes of Health (NIH), the risks from the radiation dose According to the National Institutes of Health (NIH), the risks from the radiation dose i t d ith b th h d BSGI d t 20 i t d ith b th h d BSGI d t 20 30 Ci 30 Ci associated with both mammography and BSGI procedures at 20 associated with both mammography and BSGI procedures at 20 –– 30 mCi are 30 mCi are

considered to be "minimal". considered to be "minimal".

The radiation dose from the BSGI at 20 The radiation dose from the BSGI at 20 –– 30 mCi is equivalent to living in Denver, 30 mCi is equivalent to living in Denver, Colorado for one year and is acceptable for the diagnostic population. Colorado for one year and is acceptable for the diagnostic population.

According to the drug data sheet for Cardiolite, the prescription range is from 10 to 30 According to the drug data sheet for Cardiolite, the prescription range is from 10 to 30 mCi. Therefore, if a center wishes to minimize radiation dose from this procedure, lower mCi. Therefore, if a center wishes to minimize radiation dose from this procedure, lower doses and longer imaging times can be utilized.doses and longer imaging times can be utilized.

It is important to note that this pharmaceutical has been used in cardiac imaging for It is important to note that this pharmaceutical has been used in cardiac imaging for nearly 20 years without a single reported adverse reaction to the radiation dose.nearly 20 years without a single reported adverse reaction to the radiation dose.y y g py y g p

Radiation Radiation DosimetryDosimetryAdministered

DoseEffective Dose

EquivalentScreening MMG 4 view only n/a 0 7 mSvScreening MMG - 4 view only

Does not include diagnostic MMG

n/a 0.7 mSv

BSGI (Sestamibi) 20 mCi 6.7 mSv

CT chest N/A 7.8 mSv

Coronary CT (Women) N/A 10.2 mSv

PET (F-18 FDG) 10 mCi 11.1 mSv

CT abdomen and pelvis N/A 14.7 mSv

Mammography Dosimetry: Mammography Dosimetry: American College of Radiology, www.acr.orgAmerican College of Radiology, www.acr.org. Sestamibidosimetry for BSGI. Sestamibidosimetry for BSGI: International Commission on Radiologic Protection. Radiation : International Commission on Radiologic Protection. Radiation Dose to Patients from Radiopharmaceuticals New York NY: Permamon Press; 1988 ICRP Publication 53 Cardiolite Drug Data SheDose to Patients from Radiopharmaceuticals New York NY: Permamon Press; 1988 ICRP Publication 53 Cardiolite Drug Data Sheetet Bristol Myers Squibb May 2003 Bristol Myers Squibb May 2003 FDG FDG

PET/CT 10 mCi 23.0 mSv

Dose to Patients from Radiopharmaceuticals. New York, NY: Permamon Press; 1988. ICRP Publication 53. Cardiolite Drug Data SheDose to Patients from Radiopharmaceuticals. New York, NY: Permamon Press; 1988. ICRP Publication 53. Cardiolite Drug Data Sheet.et. Bristol Myers Squibb. May 2003. Bristol Myers Squibb. May 2003. FDG FDG Dosimetry for PEMDosimetry for PEM Dosimetry Dosimetry -- FF--1818--Fluorodeoxyglucose, NUREG/CRFluorodeoxyglucose, NUREG/CR--6345, page 9, September 18, 1992.. J.E. Kalinyak, MD, PhD. "Comparison of Radioph6345, page 9, September 18, 1992.. J.E. Kalinyak, MD, PhD. "Comparison of Radiopharmaceuticals armaceuticals Used in Positron Emission Mammography (PEM) and Breast Specific Gamma Imaging (BSGI). White paper. Naviscan PET Systems, Inc.Used in Positron Emission Mammography (PEM) and Breast Specific Gamma Imaging (BSGI). White paper. Naviscan PET Systems, Inc., M, March 2007. CT of chest abdomen arch 2007. CT of chest abdomen and pelvis: Bushberg et al. The essential physics of Medical Imaging. 2and pelvis: Bushberg et al. The essential physics of Medical Imaging. 2ndnd ed. Philadelphia PA. Lippincott Williams and Wilkens; 2002 795ed. Philadelphia PA. Lippincott Williams and Wilkens; 2002 795--812. Coronary CT: Ropers et al. 812. Coronary CT: Ropers et al. Usefulness of multidetector row spiral CT for the noninvasive detection of coronary artery stenosis. PET/CT: Annals of the IUsefulness of multidetector row spiral CT for the noninvasive detection of coronary artery stenosis. PET/CT: Annals of the Intenternational Commission on Radiation Protection. rnational Commission on Radiation Protection. Dose to patients from radiopharmaceuticals . Publication 80. Tarrytown NY. Elesevier Science Inc. 1999.Dose to patients from radiopharmaceuticals . Publication 80. Tarrytown NY. Elesevier Science Inc. 1999.

The Impact of Dedicated Detectors on DoseThe Impact of Dedicated Detectors on Dose

Dedicated detectors are up to 4 times more sensitive than the standard cameras

This indicates that it should be possible to use a lower dose.

Anecdotally, some centers have used doses around 12 - 15 mCi y,

BUT remember that all of studies to date to establish effiicacy have been conducted at 20 – 30 mCi AND a lesser dose is an off label use

Carrie B. Hruska, Michael K. O’Connor and Douglas A. Collins. Comparison of small field of view gamma camera systems for scintimammography. Nucl Med Commun 26:441–445.

Dose Reduction StudyDose Reduction Studyyy As in all imaging, there is a desire to lower the dose as much as As in all imaging, there is a desire to lower the dose as much as

possible. possible.

Obviously, the risk of a missed cancer is a far greater risk to the Obviously, the risk of a missed cancer is a far greater risk to the patient than the risk of the radiation dosepatient than the risk of the radiation dose

Therefore lowering the dose to a level that decreases the Therefore lowering the dose to a level that decreases the sensitivity of the examination is not beneficial to the patientsensitivity of the examination is not beneficial to the patient

Question: Question: How far can the dose be lowered without negatively How far can the dose be lowered without negatively impacting the efficacy of this Imaging procedure?impacting the efficacy of this Imaging procedure?p g y g g pp g y g g p

Answer: Answer: No one knows, but a multiNo one knows, but a multi--center prospective trial is center prospective trial is under way to answer this questionunder way to answer this questionunder way to answer this questionunder way to answer this question

Risk vs. BenefitRisk vs. Benefit As with all medical procedures, we must evaluate the As with all medical procedures, we must evaluate the

procedure risk against the benefit to the patientprocedure risk against the benefit to the patient

Radiation risk is just one form of riskRadiation risk is just one form of risk

We use BSGI selectively in three primary populationsWe use BSGI selectively in three primary populationsPatients who have a negative or indeterminatePatients who have a negative or indeterminate–– Patients who have a negative or indeterminate Patients who have a negative or indeterminate mammogram/ultrasound and a remaining clinical concernmammogram/ultrasound and a remaining clinical concern

–– Patients at high risk for breast cancer if MMG is not sufficient Patients at high risk for breast cancer if MMG is not sufficient f i (d l diffi lt i t t)f i (d l diffi lt i t t)for screening (dense, complex, or difficult interpret)for screening (dense, complex, or difficult interpret)

–– Patients with positive mammograms or known breast cancer Patients with positive mammograms or known breast cancer diagnosis to improve treatment planning.diagnosis to improve treatment planning.g p p gg p p g

Risk vs. Benefit Cont.Risk vs. Benefit Cont. In the retrospective analysis of BSGI patients presented at RSNA In the retrospective analysis of BSGI patients presented at RSNA

in 2009, we established that BSGIin 2009, we established that BSGI BSGI detected 30 malignant and 7 highBSGI detected 30 malignant and 7 high--risk lesions in 240 patientsrisk lesions in 240 patientsBSGI detected 30 malignant and 7 highBSGI detected 30 malignant and 7 high risk lesions in 240 patients risk lesions in 240 patients

(15.4%) with (15.4%) with negative or indeterminate mammogramsnegative or indeterminate mammograms The overall sensitivity of MMG and BSGI was 71% and 93% The overall sensitivity of MMG and BSGI was 71% and 93%

respectively.respectively.

It i l th t thi i i d iIt i l th t thi i i d i It is clear that this imaging procedure is It is clear that this imaging procedure is beneficial in detecting cancers occult to beneficial in detecting cancers occult to mammography and that it improves themammography and that it improves themammography and that it improves the mammography and that it improves the management of properly selected casesmanagement of properly selected cases

The radiation risk is far outweighed by the The radiation risk is far outweighed by the b fit t l l t d ti tb fit t l l t d ti tbenefit to properly selected patientsbenefit to properly selected patients

Work is underway to lower the doseWork is underway to lower the dose

Newly diagnosed breast cancer requiring preoperative work-uprequiring preoperative work up.

Patient is claustrophobic and refused MRI leading to a recommendation for BSGI.

Courtesy of Dr. Mike Linver, X-ray Associates y , yof New Mexico, Albuquerque, NM

N l di d bNewly diagnosed breast cancer requiring preoperative work-up.

Patient is claustrophobic and refused MRI leading to a recommendation for BSGI.

Courtesy of Dr. Mike Linver, X-ray Associates of New Mexico, Albuquerque, NM

Now the patient agrees to an MRI yielding multiple

h i itenhancing sites

Courtesy of Dr. Mike Linver, X-ray Associates of New Mexicoof New Mexico, Albuquerque, NM

Results of a Multi-Center Patient Registry to Determine the Clinical Impact of Breast Specific Gamma Imaging the Clinical Impact of Breast-Specific Gamma Imaging,

a Molecular Breast Imaging Technique

Overall N = 1 042

•Evaluation of equivocal mammography and/or Ultrasound.

•Cancer surveillance in patients with a personal history of breast cancerOverall N = 1,042

Sensitivity 91%

breast cancer.

•Positive mammogram prior to biopsy to aid in biopsy target selection, particularly in patients with multiple suspicious areas

Specificity 77%**MMG Sensitivity = 71%

•Palpable mass not demonstrated in mammogram or ultrasound.

MMG Sensitivity = 71%•Radiodense breast tissue difficult to image mammographically

•Screening in high-risk patient populations

Bertrand M, Lanzkowsky L, Stern L, Weigert J. Podium Presentation Radiologic Society of North America Annual Meeting. November 29th – December 4th 2009.

Clinical Utility of Breast Specific Gamma Imaging For Clinical Utility of Breast Specific Gamma Imaging For y p g gy p g gEvaluating Disease Extent in the Evaluating Disease Extent in the Newly Diagnosed Breast Newly Diagnosed Breast

Cancer PatientCancer Patient 138 newly diagnosed cancers138 newly diagnosed cancers Found additional disease in 11% of casesFound additional disease in 11% of cases

S iti it 91 4%S iti it 91 4% Sensitivity = 91.4%Sensitivity = 91.4% Specificity = 94.2%Specificity = 94.2%

Zhou M Johnson N Gruner S Ecklund GW Muenier P Bryn S Green G et al Clinical Utility of BreastZhou M Johnson N Gruner S Ecklund GW Muenier P Bryn S Green G et al Clinical Utility of BreastZhou M, Johnson N, Gruner S, Ecklund GW, Muenier P, Bryn S, Green G, et al. Clinical Utility of Breast Zhou M, Johnson N, Gruner S, Ecklund GW, Muenier P, Bryn S, Green G, et al. Clinical Utility of Breast Specific Gamma Imaging For Evaluating Disease Extent in the Newly Diagnosed Breast Cancer Patient. Specific Gamma Imaging For Evaluating Disease Extent in the Newly Diagnosed Breast Cancer Patient. The American Journal of Surgery, Vol 197, No 2, February 2009.The American Journal of Surgery, Vol 197, No 2, February 2009.

Clinical Data SummaryClinical Data SummaryClinical Data SummaryClinical Data SummaryOf 16 papers and presentationsOf 16 papers and presentations

Total Number of patients 3494

Overall Sensitivity 92.1%Overall Specificity 78 1%Overall Specificity 78.1%

Overall PPV 57.7%Overall NPV 97.3%Overall NPV 97.3%

GammaLōc® System StereotacticStereotactic SystemSystemStereotactic Stereotactic System System ComponentsComponents

Grid SystemGrid System

Stereo Viewing Collimator System

Grid System Fiducial & Collimator Grid System Fiducial & Collimator ReferencesReferences

Grid Support

Needle Positioning

Grid

gBlock

Grid (disposable)

Fiducial Marker Source

Column and Hole Reference

Column and Hole Reference

Gamma Emitting MarkerGamma Emitting Marker

R di ti SRadioactive Source(Reusable)

St il SlSterile Sleeve(Single Use)

Assembled

Compatible with Existing Dilon 6800

Front View

Slant-hole Collimator ConceptRight ViewLeft View

LesionLesion

BreastBreast

Gamma CameraGamma Camera

Localization Slant-hole Collimator ConceptSlant hole Collimator ConceptCentered View - for validation and biopsy

Lesion

Breast

Front View

Verification with Radioactive Marker

O I i d t it th X Y Z l ti f M k S

Gamma Camera

One Image is used to monitor the X, Y, Z location of a Marker Source

Clinical ConsiderationsClinical Considerations

Sensitivity by SubgroupSensitivity by SubgroupSensitivity by SubgroupSensitivity by Subgroup** Differences are not statistically significant** Differences are not statistically significant

BSGI PEMOverall 96%DCIS 94%

Overall 90%DCIS 91%

BSGI PEM

ILC 93%Sub-centimeter 89%

ILC 75%Sub-centimeter 63%

BSGI - Brem RF. Floerke AC. Rapelyea JA. Teal C. Kelly T. Mathur V. Breast-specific gamma imaging as an adjunct imaging modality for the diagnosis of breast cancer. Radiology. 247(3):651-7, 2008 June. Brem R, et al. Breast Specific Gamma Imaging in Women with One

Suspicious or Cancerous Breast Lesion. Invasive Lobular Carcinoma: Detection with Mammography, Ultrasound, Magnetic Resonance Imaging, and Breast-specific Gamma Imaging (BSGI). 2008 Radiological Society of North America Annual Meeting.

PEM - Berg WA, Weinberg IN, Narayanan D, Lobrano ME, Ross E, Amodei L, TafraL,Adler LP, Uddo J, Stein W 3rd,Levine EA. High-resolution fluorodeoxyglucose positron emission tomography with compression ("positron emission mammography") is highly accurate in depicting primary breast cancer. Breast J. 2006 Jul-Aug;12(4):309-23.

Energy ResolutionEnergy Resolution

“Neither qualitative nor quantitative “Neither qualitative nor quantitative

gygy

Neither qualitative nor quantitative Neither qualitative nor quantitative assessment of tumor contrast in breast assessment of tumor contrast in breast phantom images provided a strong phantom images provided a strong p g p gp g p grelationship between energy resolution relationship between energy resolution and tumor contrast.”and tumor contrast.”

Carrie B. Hruska, Michael K. O'Connor. CZT detectors: How important is energy Carrie B. Hruska, Michael K. O'Connor. CZT detectors: How important is energy resolution for nuclear breast imaging? PhysicaMedica Vol 21 Sup 1: 72resolution for nuclear breast imaging? PhysicaMedica Vol 21 Sup 1: 72--75 75 resolution for nuclear breast imaging? PhysicaMedica. Vol 21, Sup 1: 72resolution for nuclear breast imaging? PhysicaMedica. Vol 21, Sup 1: 72--75. 75. 20062006

Spatial ResolutionSpatial Resolution

A i ti f th ff t f i l i b t l i A i ti f th ff t f i l i b t l i

pp

An examination of the effect of pixel size on breast lesion An examination of the effect of pixel size on breast lesion contrast.contrast.

Detectors with pixel sizes of 1.4, 2.2 and 3.2mm were Detectors with pixel sizes of 1.4, 2.2 and 3.2mm were Detectors with pixel sizes of 1.4, 2.2 and 3.2mm were Detectors with pixel sizes of 1.4, 2.2 and 3.2mm were testedtested

Conclusion, “The camera with the largest (3.2mm) crystal Conclusion, “The camera with the largest (3.2mm) crystal pitch performed better than the others tested ”pitch performed better than the others tested ”pitch performed better than the others tested…pitch performed better than the others tested…Mitali J. MoréMitali J. Moré, Patricia J. Goodale, Stan Majewski, and Mark B. Williams. , Patricia J. Goodale, Stan Majewski, and Mark B. Williams. Evaluation of Gamma Evaluation of Gamma Cameras for Use in Dedicated Breast Imaging. IEEE Trans NuclSci, 53:5; 2675Cameras for Use in Dedicated Breast Imaging. IEEE Trans NuclSci, 53:5; 2675--9. 20069. 2006

Dual Head DetectorDual Head Detector “The use of a dual“The use of a dual--head system is not absolutely necessary for acquiring head system is not absolutely necessary for acquiring

opposing views of the breast because it is possible to obtain the superior opposing views of the breast because it is possible to obtain the superior and inferior views of the CC position and medial and lateral views of the and inferior views of the CC position and medial and lateral views of the and inferior views of the CC position and medial and lateral views of the and inferior views of the CC position and medial and lateral views of the MLO position with separate acquisitions performed using only a singleMLO position with separate acquisitions performed using only a single--head head detector.”detector.”

“We realize that the cost of the molecular breast imaging system would be “We realize that the cost of the molecular breast imaging system would be increased by adding a second detector head; however, because this study increased by adding a second detector head; however, because this study was a preliminary study with a prototype system, a true costwas a preliminary study with a prototype system, a true cost––benefit ratio of benefit ratio of commercial dualcommercial dual--head molecular breast imaging compared with singlehead molecular breast imaging compared with single--head head

l l b t i i i t t b d t i d ” l l b t i i i t t b d t i d ” molecular breast imaging is yet to be determined.” molecular breast imaging is yet to be determined.”

Hruska C, Phillips SW Whaley DH, Rhodes DJ, O’Connor MK. Molecular Breast Imaging: Use of a DualHruska C, Phillips SW Whaley DH, Rhodes DJ, O’Connor MK. Molecular Breast Imaging: Use of a Dual--Head Head Dedicated Gamma Camera to Detect Small Breast Tumors. AJR:191, December 2008Dedicated Gamma Camera to Detect Small Breast Tumors. AJR:191, December 2008,,

Relative concentrationsRelative concentrationsof sestamibi inof sestamibi intissues

Cancer Cancer cellscellstissues cellscells

InflammatoryInflammatory

AtypicalAtypicalcellscells

N lN l

InflammatoryInflammatorycellscells

Normal Normal cellscells

100 100 -- 200200 180 180 -- 300300 380 380 -- 530 530 280 280 -- 400400

BSGI and PEMBSGI and PEMBSGI and PEMBSGI and PEM

Each view takes 8 Each view takes 8 –– 10 minutes.10 minutes. Usually image both breastsUsually image both breasts Usually image both breasts.Usually image both breasts. Add axillary view if suspect a cancer to Add axillary view if suspect a cancer to

look for positive lymph nodeslook for positive lymph nodeslook for positive lymph nodes.look for positive lymph nodes.

Molecular Breast ImagingMolecular Breast ImagingMolecular Breast Imaging Molecular Breast Imaging

If it is positiveIf it is positive——usually very discrete usually very discrete hot spot or spots.hot spot or spots.p pp p

If it is negativeIf it is negative——the chances of the chances of missing something is extremely smallmissing something is extremely smallmissing something is extremely small.missing something is extremely small.

Who should perform Who should perform ppBSGI?BSGI? Breast CenterBreast Center Nuclear Medicine DepartmentNuclear Medicine Department Nuclear Medicine DepartmentNuclear Medicine Department

RequirementsRequirementsRequirementsRequirements

Small room. Machine is very mobile.Small room. Machine is very mobile. Hot LabHot Lab Hot LabHot Lab License to inject isotope.License to inject isotope.

T h ll t t BREASTT h ll t t BREAST Tech excellent at BREAST Tech excellent at BREAST POSITIONING!POSITIONING!

Radiologist adept at correlating Radiologist adept at correlating Mammogram, Ultrasound, MRI, and Mammogram, Ultrasound, MRI, and BSGI.BSGI.

How is test received by How is test received by yypatients?patients? 1. Test is relatively comfortable.1. Test is relatively comfortable. 2 No compression2 No compression 2. No compression.2. No compression. 3. No claustrophobia.3. No claustrophobia.

4 C t h TV4 C t h TV 4. Can watch TV.4. Can watch TV.

55 Get resultsGet results 5. 5. Get results Get results immediately!!!!immediately!!!!

Correlation with otherCorrelation with otherstudies is essential!studies is essential!

Typical positive BSGI Typical positive BSGI study left breast upperstudy left breast upperstudy left breast upperstudy left breast upper--outer quadrantouter quadrantqq

Typical Normal StudyTypical Normal StudyTypical Normal StudyTypical Normal Study Vague Bilateral UptakeVague Bilateral UptakeVague Bilateral UptakeVague Bilateral Uptake

Hormonal ActivityHormonal Activity

6 months later off HRT

Just as in MRI, hormone influence may interfere with imaging--day 2 - 12 of cycle optimal

6 months later, off HRT

Asymmetrical patternTypical pattern Asymmetrical pattern

BBiic Focal abnormal:cs

Can be malignancyinflammation, atypiaor some benign processess or some benign processes

oInvasive ductal carcinoma

f

Breast AbscessBreast AbscessBreast AbscessBreast Abscess What size lesion can What size lesion can Molecular Imaging find?Molecular Imaging find? Many Many 3 3 --5 mm 5 mm lesions have been lesions have been

found.found. Occasionally see a 1.5 mm lesion.Occasionally see a 1.5 mm lesion. Most infiltrating lobular cancersMost infiltrating lobular cancers Most infiltrating lobular cancers Most infiltrating lobular cancers

(Frequently missed on Mammography (Frequently missed on Mammography until 5until 5 6 cm )6 cm )until 5until 5--6 cm.) 6 cm.)

5 mm lesion5 mm lesionPapillomaPapilloma Clinical IndicationsClinical IndicationsClinical IndicationsClinical Indications

Probable Breast MalignancyProbable Breast Malignancy 1 Evaluate extent of cancer1 Evaluate extent of cancer 1. Evaluate extent of cancer1. Evaluate extent of cancer 2. Evaluate for synchronous disease in 2. Evaluate for synchronous disease in

same or opposite breastsame or opposite breastsame or opposite breastsame or opposite breast ((MultifocalMultifocal or or MulticentricMulticentric Disease) Disease)

NippleNippleNi lNi lNippleNipple

Unifocal invasive ductal carcinomaUnifocal invasive ductal carcinoma

Age 60Age 60Age 60Age 60

Unifocal invasive ductalUnifocal invasive ductalUnifocal invasive ductal Unifocal invasive ductal carcinomacarcinoma

Multifocal cancerMultifocal cancerextending to nippleextending to nipple Multifocal CancerMultifocal CancerMultifocal CancerMultifocal Cancer

Positive Core BiopsyPositive Core BiopsyPositive Core BiopsyPositive Core Biopsy

Should all patients recently diagnosed Should all patients recently diagnosed with breast cancer have an with breast cancer have an MRIMRI or or BSGIBSGI before deciding on a definite before deciding on a definite surgical plan?surgical plan?g pg p

BSGI or MRI BSGI or MRI changes managementchanges management in in 1010--20% of selected cases!20% of selected cases!1010 20% of selected cases!20% of selected cases!

Personal History Personal History of of yyBreast CancerBreast Cancer

1. Suspected Recurrence1. Suspected Recurrence 2 Monitoring Response to Therapy2 Monitoring Response to Therapy 2. Monitoring Response to Therapy2. Monitoring Response to Therapy

76 year old76 year old76 year old 76 year old

Had Had benignbenign biopsy right breast in biopsy right breast in 2002. Now area of scar has changed 2002. Now area of scar has changed ggslightly.slightly.

Scar vs RecurrenceScar vs RecurrenceScar vs. RecurrenceScar vs. Recurrence

2002 2006

2002 2006

Suspicious calcifications BSGI indicates recurrenceat lumpectomy site at lumpectomy site

lumpectomy scar vs. recurrencelumpectomy scar vs. recurrence-- Normal BSGI Normal BSGI -- no recurrenceno recurrence

Response to Neoadjuvant Response to Neoadjuvant p jp jChemotherapyChemotherapy

Preoperative ChemotherapyPreoperative ChemotherapyPreoperative ChemotherapyPreoperative ChemotherapyIs this the right treatment?Is this the right treatment?

Initial study 12-07 Halfway point of chemo 3-08

Triple Negative Receptors

Before Chemo After 5Before Chemo After 5months months PEM v BSGIPEM v BSGIPEM v BSGIPEM v BSGI

PEM or BSGI can be used to assess PEM or BSGI can be used to assess breast in patient diagnosed with breast in patient diagnosed with p gp gbreast cancer.breast cancer.

At this time PEM can not beAt this time PEM can not be At this time PEM can not be At this time PEM can not be reimbursed for workreimbursed for work--up of a patient up of a patient with abnormal mammogramwith abnormal mammogramwith abnormal mammogram, with abnormal mammogram, ultrasound, or unexplained symptoms, ultrasound, or unexplained symptoms, but with no personal history of breastbut with no personal history of breastbut with no personal history of breast but with no personal history of breast cancer. cancer.

Daily Uses Daily Uses in patients in patients yy ppwith no Breast Cancerwith no Breast Cancer 1. Bloody Nipple Discharge1. Bloody Nipple Discharge 2 Unexplained Palpable Mass2 Unexplained Palpable Mass 2. Unexplained Palpable Mass2. Unexplained Palpable Mass 3. Bilateral Masses3. Bilateral Masses--Which should be Which should be

biopsied?biopsied?biopsied?biopsied? 4. Calcifications4. Calcifications-- Which should be Which should be

bi i d?bi i d?biopsied? biopsied? 5. Cysts Obscuring Underlying Tissue. 5. Cysts Obscuring Underlying Tissue.

6. Extremely Dense Breasts plus 6. Extremely Dense Breasts plus Breast Cancer Gene or Strong Family Breast Cancer Gene or Strong Family g yg yHistory.History.

7 Free Silicone Injections7 Free Silicone Injections 7. Free Silicone Injections7. Free Silicone Injections 8. Breast Implants 8. Breast Implants

9 A t i D it if ld9 A t i D it if ld 9. Asymmetric Density esp. if no older 9. Asymmetric Density esp. if no older Mammogram. Mammogram.

Bloody Nipple DischargeBloody Nipple DischargeBloody Nipple DischargeBloody Nipple Discharge 55 year old patient55 year old patient55 year old patient 55 year old patient with persistent with persistent

l bl b litl bl b litpalpable abnormality palpable abnormality upper outer quadrant upper outer quadrant right breastright breastMammography, ultrasound,Mammography, ultrasound,Mammography, ultrasound,Mammography, ultrasound,and BSGI normaland BSGI normal

Biopsy concordant Biopsy concordant --t i lit i lino atypia or malignancy no atypia or malignancy

Bilateral MassesBilateral Masses

Which ones need biopsyWhich ones need biopsyWhich ones need biopsy Which ones need biopsy

Bilateral multifocal phyllodes tumorsBilateral multifocal phyllodes tumors

Multiple FibroadenomasMultiple FibroadenomasMultiple FibroadenomasMultiple Fibroadenomas Which calcifications Which calcifications should we worry about?should we worry about?

MicrocalcificationsMicrocalcificationsMicrocalcificationsMicrocalcificationsof extensive inof extensive in--situsitumalignancymalignancy

Technically difficultTechnically difficultyymammogrammammogram

1. Radiodense breasts1. Radiodense breasts 2 Implants2 Implants 2. Implants2. Implants 3. Free Silicone3. Free Silicone

Dense breastsDense breastsDense breasts Dense breasts Positive family historyPositive family history

333 mm 3 mm IDCIDCIDCaIDCa

Free SiliconeFree SiliconeFree SiliconeFree Silicone

Normal

Invvasiiv

LimitationsLimitations of BSGIof BSGILimitationsLimitations of BSGIof BSGI

Cases with vague patchy uptake Cases with vague patchy uptake bilaterally.bilaterally.yy

LimitationsLimitations of BSGIof BSGILimitationsLimitations of BSGIof BSGI

Immediately following surgeryImmediately following surgery, area , area will be positive and may stay positive will be positive and may stay positive for up to a year.for up to a year.

Can not assess for Can not assess for clear marginsclear margins.. Can not assess for Can not assess for posterior chest wall posterior chest wall

or pectoral muscle or pectoral muscle involvement.involvement. Even with excellent positioning may Even with excellent positioning may

miss cancers close to chest wall or miss cancers close to chest wall or deep in axilla.deep in axilla.

Uptake along surgicalUptake along surgicalp g gp g gmarginmargin Things BSGI cannot doThings BSGI cannot doThings BSGI cannot do.Things BSGI cannot do.

100% sensitivity and specificity100% sensitivity and specificity Resolve lesions under 2mmResolve lesions under 2mm Resolve lesions under 2mm.Resolve lesions under 2mm. Image close to chest wallImage close to chest wall

It Let’s You Sleep AtIt Let’s You Sleep AtppNightNight

We would like to make the diagnosis We would like to make the diagnosis as quickly and as accurately as as quickly and as accurately as possible.possible.

We need to decrease We need to decrease patient’s patient’s anxietyanxiety as quickly and accurately as as quickly and accurately as possible.possible.

We need to decrease the number of We need to decrease the number of BIRADS 3 (indeterminate) studies and BIRADS 3 (indeterminate) studies and number of biopsiesnumber of biopsiesnumber of biopsies. number of biopsies.

Bringing New Excitement Bringing New Excitement g gg ginto Breast Imaginginto Breast Imaging Multimodality!Multimodality! Back to patient Back to patient pp

contact!contact! Being a detective.Being a detective. Following trail all Following trail all

the way to a the way to a conclusion!conclusion!

Giving good advice Giving good advice ddto patients and to patients and

other physicians.other physicians.