Molecular Breast Imaging: History and Recent Developments

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1 Molecular Breast Imaging: History and Recent Developments Associate Professor, Department of Imaging Physics The University of Texas MD Anderson Cancer Center, Houston, Texas Educational Objectives 1. To become familiar with the historical developments on MBI 2. To understand the technological advances in MBI systems that leads to improved image quality and lower radiation doses 3. To become familiar with clinical role of MBI for patients with breast cancer Spring AAPM Meeting March 6, Screening Mammography: Pros and Cons Mammography overall sensitivity ~79% & specificity ~90% (NCI, 2012) Screening mammography believed to be an important factor in recent declines in breast cancer mortality (Tabar, Cancer 2001) However, breast cancer is still the second leading cause of cancerrelated deaths for women in USA improved methods to fight breast cancer needed! Emission Imaging A Clinical Example MG MBI About 40% of women undergoing mammography screening have dense breast tissue (Jackson, Radiology 1993). High breast density is considered a risk factor for breast cancer (Boyd, NEJM 2007). X ray mammography has lower sensitivity for dense breasts. Sensitivity for BI RADS 1,2,3,4 are 88%,82%,69%,62% (Halladay, AJR 2010) Improved screening techniques, especially for women at risk and those with dense breasts, needed! Transmission imaging focuses on anatomy rather than function Screening MG was interpreted negative for disease. MBI indicates a small lesion in the lower quadrant. Lesion was also visible in MRI and confirmed at surgery as a 9 mm DCIS. (O Connor, Exp Rev 2009) 3 4 1

2 Scintimammography Tc 99m sestamibi approved by FDA for breast imaging in mci administered intravenously, ~5 min uptake, Planar images 99mTc sestamibi specifically binds to mitochondria in cells. The density of mitochondria is a marker of cellular proliferative activity a hallmark of cancer cells Scintimammography Single head conventional gamma camera 10 min lateral planar image of suspect breast Sub optimal image acquisition conditions Proximity, collimation, detectors, non target organ uptake Indicated for: Use as an adjunct diagnostic modality after mammography to assist in the evaluation of breast lesions in patients with an abnormal mammogram or a palpable breast mass Not indicated for: breast cancer screening, to confirm the presence or absence of malignancy, and not an alternative to biopsy (SNM Practice Guideline for Breast Scintigraphy, JNMT 38, 2010) (Taillefer, Sem NM, 2005) 5 6 Scintimammography Several large multicenter studies undertaken in late 1990s Taillefer: Sem Nucl Med 29:16, 1999 (2009 patients) Sensitivity = 85%, specificity = 89% Sensitivity ~55% for masses <1.5 cm Brem: J Nucl Med 43:909, 2002 Sensitivity 35 64% for lesions <1 cm Impact of Tumor Size on Metastatic Disease % with Metastatic Disease % Aust. Inst. Health Welfare, Oct 2007 <10 mm: 5-year survival = 98% 30 mm : 5-year survival = 70% 33% 45% 52% 60% 70% 0 < >5 Slide courtesy M. O Connor, Mayo Tumor size (cm) 7 8 2

3 Key advances in NM breast imaging Breast specific gamma camera imaging geometry isolation of breast from nearby organs with avid uptake Improved spatial resolution compared to conventional gamma cameras reduction in the breast to detector distance through direct contact and application of mild breast compression use of pixelated arrays of small detector elements Improved sensitivity compared to conventional gamma cameras Solid state detectors (CZT) with higher energy resolution Collimation matched to detector pixels Collimator design optimized for near field imaging Evolution of Breast Imaging in Nuclear Medicine Conventional NaI Gamma Camera Scintimammography 1990 s Multicrystal Sodium Iodide BSGI 2000 s 2010 s Cadmium Zinc Telluride (CZT) MBI 9 10 Breast Specific Gamma Imaging (BSGI) Dilon Technologies Inc. (Newport News, VA) Dilon 6800 system single gamma camera head array of NaI crystals (3 mm x 3 mm x 6 mm) coupled to an array of position sensitive PMTs active detector area 20 cm x 15 cm, image matrix 64 x 64 low energy, high sensitivity collimator; 1.9 mm hexagonal holes in shape with a hole Dilon 6800 Acella model used CsI crystals (3.2mm x 3.2 mm) coupled to solid state photo diodes and 25 cm x 20 cm FOV Normal Case (Seigal et al, Breast, 2012) BSGI Clinical Cases Abnormal Case

4 Clinical Findings from BSGI highlights George Washington University (Brem et al, Radiology, 2008) 146 cases: Sensitivity of 96% and Specificity of 59% smallest invasive cancer and DCIS detected were ~1 mm BSGI helped detect occult cancer not visualized at mammography or ultrasonography in six patients Henry Ford Hospital (Seigal et al, Breast, 2012) 416 cases: Sensitivity of 93% and specificity of 79% BMI is both a sensitive and specific test useful as an adjunct to standard breast imaging modalities for problem solving in indeterminate cases Advances from Mayo Clinic Michael O Connor and Carrie Hruska have led a number of investigations with significant impact of the field of MBI Evaluated solid state CZT detectors Collimator design optimized for near field imaging Evaluated dual headed detector system Conducted a number of clinical studies Collimation for MBI with Square Pixels GE Discovery NM750b Conventional: Hexagonal hole 2.5 mm diameter Matched Hole: Square hole matched to pixel size FWHM 3 cm Det Pass Det Pass GE Specs: FWHM 3 cm = 5 mm Sensitivity (counts/bq) increased by % Collimator optimized for near field imaging

5 Comparison of Breast Phantom Images System specific collimators and energy window Breast Thickness 6 cm Tumor depth 3 cm TBR 5.6:1 (Hruska et al, NM Comm, 2005) Dual headed MBI system 150 patients with BI RADS 4 or 5 and lesions <2 cm identified on mammography or sonography and scheduled for biopsy underwent MBI 128 cancers were confirmed in 88 patients Averaging the results from the three blinded readers Sensitivity Dual head Single head Size < 2 cm Size < 1 cm (Hruska et al., AJR 191, 2008) MBI Clinical Case Measured energy spectrum with CZT (Hruska et al., AJR 191, 2008) (Hruska et al., Med Phys, 2012)

6 Overall Gain from System Optimization (Hruska et al., Med Phys, 2012) (Hruska et al, NM Comm, 2005) MDACC experience: GE MBI system x2.9 gain in sensitivity compared to conventional gamma camera GE Discovery NM 750b Gamma Medica LumaGEM

7 MBI System Summary Gamma Medica General Electric Model LumaGem Discovery NM 750b FOV 20 cm x 16 cm 20 cm x 20 cm Pixel Size 1.6 mm 2.5 mm Energy kev (%) 4^ 5.7 Chest wall side dead space 7 8 mm 7 8 mm Sensitivity* (cpm/uci) 908^ 586 (FWHM mm) 3.1^ 4.75 Dual headed CZT pixilated detectors mounted on modified mammography gantry *values shown are for the optimized collimators ^manufacture specs Can we decrease the Activity? Dual headed MBI systems have improved sensitivity Matched hole collimator design Wide energy window for imaging Dual detectors Answer is YES mci (BSGI) to 8 mci (MBI) Phantom Images lesions at 1 cm, uptake 20:1, Optimized Collimator and Wide Energy Window Phantom Images lesions at 3 cm, uptake 20:1, Optimized Collimator and Wide Energy Window Gamma Medica Gamma Medica GE GE (Hruska et al., Med Phys, 2012) (Hruska et al., Med Phys, 2012)

8 MBI Radiation Doses Clinical Workflow Radiation absorbed dose to patient with MBI is proportional to the administered activity MBI mean breast dose is ~0.53 mgy for 8 mci admin. activity; that is lower than MDG for a screening MG (typically 2 3 mgy for a 5 cm thick compressed breast) However, MBI delivers radiation dose to whole body MBI effective dose ~2.6 msv for 8 mci admin. activity; compared to 2 view digital MG effective dose ~0.5 msv MG MBI Background Radiation Dose/Activity 4 mgy 8 20mCi Effective dose / 3 / 4.5 (msv) Mortality (per 10 5 ) / 1010 / mci 99mTc sestamibi administered intravenously Uptake time ~5 min 2 views of each breast similar to mammography imaging CC and MLO views Planar images in each view for 10 min/view Clinical exam completed in 1 hour time slot 2 3 min prep and dose administration 5 min uptake time 40 minutes of data acquisition 5 8 minute time between views 5 min room clean up (O Connor, Med Phys 2010) Variables affecting Sestamibi Uptake BSGI/MBI Clinical Studies Fasting increases uptake by ~25% Peripheral warming increases uptake by ~20% Exercise decreased uptake by ~35% Uptake did not correlate with a patient s height, weight, or breast thickness Emission imaging (MBI/BSGI) has high sensitivity (outperforms MG and similar to MR) and high specificity (outperforms MG and MR) Head to head screening trial of over 1000 asymptomatic patients MBI and MG had similar specificity (above 90%) but MBI demonstrated higher sensitivity, 83% versus 25% (Rhodes, Radiology 2011) In patients with indeterminate lesions, BSGI and MRI were both reported to have similar sensitivity (over 90%) but BSGI demonstrated higher specificity, 71% versus 25% (Brem, BreastJ 2007) Emission imaging has been proven to alter patient management after mammograms (O Connor et al., JNMT, 2015) In patients with known breast cancer, BSGI detected additional breast cancers in 9% of patients and 22% of patients had a surgical management change because of BSGI findings (Killelea, AJSurg 2009) Retrospective analysis showed 86% of patient with BI RADS 4 could have avoided biopsy completely because of negative BSGI. Overall, clinical management was changed significantly in 14.2%, with another 6.3% in whom a negative BSGI could have prevented a biopsy (Zhou, AJSurg 2008)

9 Clinical Impact of MBI Anecdotal finding of breast cancer in asymptomatic patients Female patients undergoing MPI were asked to participate in MBI evaluation BC detected in asymptomatic patients MBI is being explored for use as indicator of response for patients undergoing neo adjuvant chemotherapy Prospective clinical trial underway at MDACC Summary MBI is an interesting imaging system from physics perspective MBI is a promising diagnostic imaging modality poised to make clinical impact Quantitation of uptake and role in clinical management of patient is under investigation