Low Dose Molecular Breast Imaging

Transcription

1 Low Dose Molecular Breast Imaging Dr. M.K. O Connor Conflict of Interest Royalties - Gamma Medica Research funding GE Healthcare Research support MTTI Michael O Connor, Ph.D Dept. of Radiology Mayo Clinic This work has been funded in part by the following: National Institute of Health Dept. of Defense Susan G Komen Foundation Mayo Foundation Friends for an Earlier Breast Cancer Test Breast Density Classification ACR BI-RADS (qualitative score) Used by radiologists as part of routine practice BI-RADS 1 BI-RADS 2 BI-RADS 3 BI-RADS 4 <25% 25-49% 50-74% 75% Sens = 88% 82% 69% 62% Breast Density Comparative Relative Risks Risk factor Relative risk BRCA mutation 20 Lobular carcinoma in situ 8-10 Dense breast parenchyma 4-6 Personal history of breast cancer 3-4 Family history (1 relative) 2.1 Postmenopausal obesity 1.5 Mammographic density is perhaps the most undervalued and underutilized risk in studies investigating the causes of BC. Breast Density Legislation Connecticut enacted similar legislation in 2009 and a comparable breast density patient education bill, SB 173, is scheduled to be heard in the California Assembly this month.

2 Sensitivity of Mammogram, US, and MRI in Women at Increased Risk Subjects Sensitivity Sensitivity Sensitivity Author/year Country (no.) MMG (%) US (%) MRI (%) Kuhl, 2000 Germany Warner, 2004 Canada Kriege, 2004 Netherlands 1, NA 71 Kuhl, 2005 Germany Leach 2005 U.K NA 77 Sardanelli, ACRIN Year Screening Study of Ultrasound and Mammography in 2500 High-Risk Women 41 cancers detected 20 by mammography (sens 50%) 20 by ultrasound (sens 50%) Mammography: 3% biopsy, 29% positive Ultrasound: 5% biopsy, 9% positive Study PI Wendie Berg: "Women contemplating breast ultrasound screening must be aware of the substantial risk of false positives Study Co-I Etta Pisano: based on the study results, it is difficult to determine whether screening ultrasound is worthwhile Breast MRI Poor specificity (highly variable: 50% - 90%) Patient acceptance of MRI? ACRIN 6666 trial 42% declined free MRI (25% due to claustrophobia) Molecular Imaging of the Breast PEM (Positron Emission Mammography) Coincidence detection using 2 scanning arrays of LYSO crystals Clinical unit developed by Naviscan BSGI (Breast Specific Gamma Imaging) Single detector, multicrystal NaI based gamma camera Developed by Dilon Technologies MBI (Molecular Breast Imaging) Dual detector Cadmium Zinc Telluride based gamma cameras Clinical units developed by Gamma Medica and GE Healthcare Expensive (~10 times that of mammography) PEM (Positron Emission Mammography) FOV: 16 cm x 24 cm 2 scanning arrays of LYSO 2.4 mm resolution (in plane) 8.0 mm resolution (cross-plane) (JNM 2009;50: ) Patient fasting 4-6 hr. Inject 10 mci F-18 FDG Wait ~60 minutes Obtain CC / MLO views Scan time ~10 minutes / view Molecular Imaging of the Breast PEM (Positron Emission Mammography) Coincidence detection using 2 scanning arrays of LYSO crystals Clinical unit developed by Naviscan BSGI (Breast Specific Gamma Imaging) Single detector, multicrystal NaI based gamma camera Developed by Dilon Technologies MBI (Molecular Breast Imaging) Dual detector Cadmium Zinc Telluride based gamma cameras Clinical units developed by Gamma Medica and GE Healthcare

3 BSGI (Breast Specific Gamma Imaging) FOV: 15 cm x 20 cm Single array of NaI crystals 3 mm intrinsic resolution ~18% energy resolution No patient fasting required Inject mci Tc-99m sestamibi Image ~5 minutes post injection Obtain CC / MLO views Scan time ~10 minutes / view Molecular Imaging of the Breast PEM (Positron Emission Mammography) Coincidence detection using 2 scanning arrays of LYSO crystals Clinical unit developed by Naviscan BSGI (Breast Specific Gamma Imaging) Single detector, multicrystal NaI based gamma camera Developed by Dilon Technologies MBI (Molecular Breast Imaging) Dual detector Cadmium Zinc Telluride based gamma cameras Clinical units developed by Gamma Medica and GE Healthcare Breast Phantom: Comparison between Systems* Tumor Depth 1cm *Hruska CB, et al. Nucl Med Commun, 2005; 26: Cadmium Zinc Telluride (CZT) Detector 2.54 cm 3 cm 5 cm Excellent Intrinsic Resolution = 1.6 mm / 2.5 mm Excellent Energy Resolution 4.0% / 6.5% Can be operated at room temp No dead space ideal for breast imaging Expensive currently limited to small field of view detectors MC-NaI NaI CZT MC-CsI First commercial systems using CZT developed for nuclear cardiology Molecular Breast Imaging Procedure MBI Systems Currently at Mayo Clinic Patient receives an IV injection of a radiotracer (Tc-99m sestamibi) The tracer preferentially accumulates in cancer cells and is not influenced by breast density The breast is lightly compressed between the 2 gamma cameras, only light pain-free compression is necessary Imaging starts ~5 minutes post injection. Acquire CC and MLO views of each breast for 10 minutes / view GE Research Unit GM-I Research Unit GM-I Clinical Unit

4 Can MBI find lesions not visible on mammography? Can MBI find lesions not visible on mammography? 1.1cm nodular density in upper inner right breast 9.5cm from the nipple 2 x 1 cm IDC with multiple satellite lesions confirmed as DCIS at surgery Comparison of Screening MBI and Mammography ~1000 patients - asymptomatic Compare MBI and mammography in patients with dense breasts at increased risk of breast cancer MBI performed with 20 mci Tc-99m sestamibi Breast status 12-months Question is MBI a viable screening adjunct to mammography in patients with dense breasts? Diagnostic accuracy of screening mammography and MBI Sensitivity (all cancers) Sensitivity (Invasive cancers) Sensitivity (DCIS) Specificity Recall Rate Mammography alone 25% (3/12) 25% (2/8) 25% (1/4) 91% (839/925) 9.5% (89/936) MBI alone 83% (10/12) 100% (8/8) 50% (2/4) 93% (861/925) 7.8% (73/936) Mammography plus MBI 92% (11/12) 100% (8/8) 75% (3/4) 85% (789/925) 16% (146/936) PPV 18 % (3/17) 28% (10/36) 24% (11/45) Rhodes et al, Radiology 2011;258: Mammographically occult cancers detected on MBI 10 mm + 16 mm IDC 9 mm ILC 9 mm IDC 17 mm IDC + DCIS 7 mm tubulolobular ca 9 mm DCIS 13.5 mm ILC (total extent 5.1 cm)

5 Hendrick R.E. Radiation Doses and Cancer Risks from Breast Imaging Studies Radiology Oct; 257(1): O'Connor MK, Li H, Rhodes DJ, Hruska CB, Clancy CB, Vetter RJ. Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast. Med Phys Dec;37(12): Relative Radiation Risks Radiation risk to patients Mammogram PEM (10 mci F-18 FDG) BSGI (25-30 mci Tc-99m mibi) MBI (20 mci Tc-99m mibi) ~ 0.5 msv ~ 7 msv ~ 9 msv ~ 6 msv For pop. of 100,000 women undergoing above procedures at age 40, estimated cancer mortality Mammogram ~ 2 PEM (10 mci F-18 FDG) ~ 30 BSGI (25-30 mci Tc-99m mibi) ~ 35 MBI (20 mci Tc-99m mibi) ~ 24 Where does the estimate of cancer mortality come from? Based on Table 12D from BEIR VII 100,000 women aged 30 Single dose of 100 mgy Over their lifetime Risk Models range of plausible values for LAR is labeled a subjective confidence interval to emphasize its dependence on opinions in addition to direct numerical observation (BEIR VII, page 278) Lifetime Attributable Risk (LAR) Because of the various sources of uncertainty it is important to regard specific estimates of LAR with a healthy skepticism, placing more faith in a range of possible values (BEIR VII, page 278)

6 Relative Radiation Risks For pop. of 100,000 women exposed to naturally occurring background radiation from age 0-80, estimated cancer mortality Background radiation U.S. Average (3.1 msv/year) ~1010 Colorado (~4.5 msv/year) ~1460 Florida (~2.5 msv/year) ~ 810 Cumulative Cancer Mortality Cancer mortality in 100,000 subjects U.S. Cancer Mortality Minnesota - 3 msv/year Colorado msv/year 50 msv at age Age(years) Estimated deaths due to background radiation. No epidemiological evidence to support these numbers 240 deaths MBI: Implications for Radiation Exposure to the Technologist from 8 patients / day, 20 mci / patient Radiation Dose Reduction Annual Technologist Dose mrem MBI Tech General NMT Cardiology NMT Radiographer Reduce dose / increase scan time? - already at ~40 minutes!! Improve the technology - detector / collimator optimization - energy window optimization - noise reduction algorithms - composite image from opposing detectors Pletta CK, et al. J Nucl Med 2009; 50 (Suppl 2): 428P. Molecular Breast Imaging Detector / Collimator Optimization Optimal pixel size for near-field imaging (0-3 cm) Clinical studies show average breast thickness = 6 cm Hence each collimator optimized over range 0 3 cm 100% 65% Monte Carlo simulations (MCNP) used to optimize detector and collimator design What is the optimal pixel size and collimation to achieve a spatial resolution = 5 mm at 3 cm? 45% 0.30

7 Molecular Breast Imaging Conventional Collimation CZT: 1.6 x 1.6 mm pixel Hexagonal hole Collimator: 2.5 mm hole diameter Molecular Breast Imaging Conventional Collimation CZT: 1.6 x 1.6 mm pixel Square hole Collimator: ~1.6 mm hole diameter Molecular Breast Imaging Collimator specifications Results from Simulation Better 3 cm Molecular Breast Imaging Matched Collimation on CZT detectors Tungsten collimator Square holes Each hole matched to individual pixel on CZT detector Factor of ~2 gain in sensitivity expected Molecular Breast Imaging Effect of Optimal Collimation CZT Detector MBI Radiation Dose Reduction Four dose reduction techniques have been developed and evaluated in order to reduce the administered dose of Tc- 99m sestamibi needed for MBI - collimator optimization - energy window optimization - noise reduction algorithms - composite image from opposing detectors

8 Wide energy window ( kev) ~1.4 gain in sensitivity System sensitivity effect of collimation and energy window Detector CZT 1.6 mm pixel Collimator Energy Window counts/ min/μci Relative gain in counts/pixel Standard Standard, 140 ± 10% Standard Wide, kev Tungsten design Standard 140 ± 10% Tungsten design Wide, kev GMI 1 cm CZT 2.5 mm pixel Standard Standard, 140 ± 10% Standard Wide, kev optimized design Standard 140 ± 10% optimized design Wide, kev GMI 3 cm

9 Contrast to Noise Ratio Lumagem 3200s Contrast to Noise Ratio Discovery 750b MBI Dose Reduction Comparison of count densities in patient studies MBI Dose Reduction Relative Gain = System # Studies Ratio of Cts (New: Old) GM CZT Dose 20 mci 8 mci MBI Radiation Dose Reduction Four dose reduction techniques have been developed and evaluated in order to reduce the administered dose of Tc- 99m sestamibi needed for MBI - collimator optimization - energy window optimization - noise reduction algorithms - composite image from opposing detectors Noise Reduction / Combined Images from Opposite Detectors Combined Images: Gaussian Neighborhood Geometric Mean (GNGM) Noise Reduction: Non-Local Means (NLM) denoising filter Wide Beam Reconstruction (UltraSPECT) Image Generation & analysis Filter parameters and order of application of noise reduction algorithms yet to be optimized

10 Gaussian Neighborhood / Geometric Mean Algorithm Comparison of Noise Reduction algorithms 8 mci Raw data 4 mci GNGM / NLM 4 mci WBR Question is low-dose MBI (~4 mci) a viable screening adjunct to mammography in patients with dense breasts? Compare MBI and mammography in asymptomatic patients with dense breasts on prior mammogram 2400 patients over next 2 years 1100 patients imaged as of 7/25/11 14/15 cancers detected on MBI 1/15 cancer detected on mammography 1 cancer missed by MBI and mammography Screening Mammogram 2 cm IDC MBI (positive) Screening Mammogram MBI (20 mci) March 2008 MBI (4 mci) (positive) March 2011

11 Screening Mammogram MBI (4 mci) (positive) Ultrasound 6.5 mm Invasive Tubular carcinoma Screening Mammogram MBI (2 mci) (positive) Ultrasound ~3 cm Invasive Lobular carcinoma Screening Mammogram MBI (2 mci) MBI Multifocal DCIS with ADH Advantages of MBI Compared to mammography: Higher sensitivity in dense breasts Comparable radiation burden to the body Less compression, improved patient comfort Compared to MRI Comparable sensitivity, better specificity Offers option if contraindication to MRI (claustrophobia, pacemaker, clips) Avoids gadolinium and potential for NSF Easy to interpret 8 images vs 1000s for MRI 5-7 fold less expensive than MRI Screening for Breast Cancer Mammography has proven to be an excellent screening technique for the majority of women Sub-optimal in women with dense breast tissue Alternative techniques are required Possible techniques include ultrasound, MRI and low-dose molecular imaging Cost and specificity will be key factors to acceptance of any adjunct screening technique