Breast Cancer Imaging Devices

Renee M. Moadel, MD, MSc

Conventional mammography is a screening procedure constrained by low specicity in the detection of breast cancer. Approximately 40% of women undergoing mammography screening have dense breast tissue, and conventional mammographic imaging has a sensitivity range of only 50%-85% for malignant lesions. Magnetic resonance imaging (MRI) is now recommended for breast cancer screening in high-risk patients. However, approximately 15% of patients cannot tolerate MRI. These are the clinical situations in which positron emission mammography (PEM) and breast-specic gamma (BSG) camera systems fulll a need for primary breast cancer imaging. Because breast cancer is the most common malignancy and the second most common cause of cancer death among women, many nuclear medicine imaging techniques are essential in the evaluation and therapy of patients with this disease. Nuclear medicine surgical techniques consist of sentinel lymph node localization and the use of radiolabeled seeds for intraoperative localization of nonpalpable breast cancers. The Food and Drug Administration (FDA) has approved the PEM Flex Solo II scanner, which has the capability for stereotactic biopsy, with an array of pixelated lutetium yttrium orthosilicate (LYSO) crystals, position-sensitive photomultiplier tubes (PS-PMT), and a spatial resolution of 2.4 mm. Clear PEM is a scanner in development with cerium-doped LYSO (LYSO:Ce) crystals, multipixel avalanche photodiodes, depth of interaction measurement with a resolution of 1.3 mm. The Dilon 6800 Gamma Camera is a BSG device approved by the FDA with stereotactic biopsy guidance capability, a pixelated array of sodium iodide crystals, PS-PMTs, and an extrinsic spatial resolution of 6 mm at 3 cm from the camera. GE has just received clearance from the FDA for a molecular breast imaging camera, the Discovery NM 750b, with pixelated cadmium zinc telluride crystals, semiconductor photoelements and an extrinsic resolution of 3.5 mm at 3 cm. The Society of Nuclear Medicine has issued guidelines for BSG camera image interpretation recommendations and clinical indications. Different crystals and camera architectures are under investigation to further improve resolution for both PEM and BSG imaging. Semin Nucl Med 41:229-241 2011 Elsevier Inc. All rights reserved.

t is advantageous to have a screening procedure such as conventional mammography for breast cancer, but unfortunately this imaging modality has a low specicity. Consequently, a large number of unnecessary procedures ensue to evaluate mammographically suspicious lesions.1 Imaging techniques and devices have been developed to either attempt to replace mammography or to further evaluate suspect lesions. Magnetic resonance imaging (MRI) is now recommended for breast cancer screening in high-risk patients.2 Although breast MRI is an optimal imaging modality for patients at high risk of breast cancer or for evaluation of mam-

Department of Nuclear Medicine, Monteore Medical Park, Bronx, NY. Address reprint requests to Renee M. Moadel, MD, MSc, Department of Nuclear Medicine, Monteore Medical Park, 1695A Eastchester Road, Bronx, NY 10461. E-mail: rmoadel@monteore.org

mographically suspicious lesions,3 approximately 15% of patients cannot tolerate this procedure because of claustrophobia, renal disease, metallic implants, body habitus, or their general medical condition.4 Approximately 40% of women undergoing mammography screening have dense breast tissue,5 and conventional mammographic imaging has a sensitivity range of only 50%-85% for malignant lesions.6 These limitations create a need for alternative imaging modalities, creating a role for nuclear medicine. 99mTc-sestamethoxyisobutylisonitrile (MIBI) and 18F-2-deoxy-2-uoroD-glucose (FDG) radiotracer dosimetry are associated with lifetime attributable risk of cancer that is an order of magnitude greater than that of conventional mammography; thus, it is doubtful that modalities that use these tracers would become screening tools.7 However, the risk benet ratio is greater in women with dense breasts and/or suspected lesions.8 Positron emission mammography (PEM) and breast229

0001-2998/11/$-see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semnuclmed.2010.12.005

230 specic gamma (BSG) camera systems that have stereotactic biopsy guidance capability are now approved by the FDA. Breast positron emission tomography (PET) combined with MRI is currently investigational. Because breast cancer is the most common malignancy and the second most common cause of cancer death among women,9 creating a signicant need for improved imaging modalities. Nuclear medicine techniques include PET/CT with FDG and other investigational tracers and planar and/or single-photon emission computed tomography (SPECT/CT) imaging with 99mTc-methylene diphosphonate for evaluation of bone metastases. Nuclear medicine surgical techniques consist of sentinel lymph node (SLN) localization and the use of radiolabeled seeds for intraoperative localization of nonpalpable breast cancers. Microspheres containing 90yttrium (90Y) are used to treat extramammary hepatic metastases.

R.M. Moadel
to generate 3-dimensional tomographic breast images. Reconstruction is performed with a maximum-likelihood expectation algorithm, and no corrections are made for scatter or randoms. Images produced have a pixel size of 1.2 mm and 12 or 24 planes parallel to the detector surfaces. This camera has a spatial resolution of 2.4 mm, and there is large variation close to the edge of the eld of view as tested by MacDonald et al.11 This resolution should allow the detection of 4-mm lesions with a 10:1 lesion to background concentration and 6- to 7-mm lesions with a 4:1 concentration, making this system clinically relevant. The capability for stereotactic biopsy is commercially available whereby there is visualization of PEM positive tumor removal (Fig. 2), and a clinical trial is currently under way to determine the efcacy and patient convenience for this procedure.12 Clear-PEM is a scanner in development by the Portuguese Consortium under the framework of the Crystal Clear Collaboration at CERN and uses a matrix of cerium-doped LYSO (LYSO:Ce) crystals, with a high Z, and rapid scintillation. Each crystal has a dimension of 2 2 20mm3 and is accompanied by a multipixel avalanche photodiode (APD), which is small enough to be congured in a 1:1 ratio. However, the APDs are arranged on the ends of each crystal in a two-to-one conguration, creating a double-readout schema. This enables a depth of interaction (DOI) measurement, which is determined from the asymmetry of the light collected on 2 APDs, and impacts image sharpness. The coincidence time resolution at 511 keV is 5.2 ns, and the energy resolution is 16%. Images are reconstructed with a 3-dimensional ordered subset expectationmaximization algorithm with deconvolution, no correction is made for scatter or randoms, and the overall resolution of the system is 1.3 mm (Fig. 3). Clear-PEM is currently undergoing clinical trials in Portugal,13,14 and the development of Clear-PEM with ultrasound is underway (Fig. 4). To further improve resolution, other crystals and camera architectures are being developed. Cerium-doped yttrium aluminum perovskit (YAP:Ce) is a medium Z material with a photo-fraction of only 4% at 511 keV; however, there are suggested mechanisms for opening up the energy window and correcting for Compton scatter. A prototype with a pixelated array of YAP:Ce coupled to position sensitive photomultiplier tubes (PS-PMT) has an intrinsic resolution of 1.4 mm.15 Cadmium zinc telluride (CZT) has high-energy resolution and a system with pixelated crystal panels has an 8 ns coincidence time window and an intrinsic spatial resolution of 1.0 mm.16 Another novel design uses an 8 8 array of 0.91 0.91 1mm3 LYSO crystals coupled with two PS-APDs. These resultant modules are then stacked perpendicular to the source of photons (ie, the 1 mm edge meets the photons) so that a depth of interaction can be measured, and the intrinsic resolution of this system is 0.837 mm with a 3 ns coincidence time resolution.17 The use of cerium-doped Lanthanum tri-bromide crystal (LaBr3:Ce), with a time resolution of 300-500 ps, could incorporate time-of-ight into a PEM system and further improve image sharpness. Silicon PMs are receiving increasing attention because of their compat-

Positron Emission Mammography

Instrumentation
Whole-body PET and PET/CT systems with FDG do not have the resolution to detect subcentimeter primary breast tumors or regional lymphadenopathy10; thus, PEM was developed to improve the resolution constraints of the whole-body systems. PEM uses 2 detectors arranged in a similar conguration to conventional mammography. The PEM Flex Solo II scanner (Naviscan PET Systems, Inc; Fig. 1), which is FDA approved, has two 6 16.4-cm detectors that can view up to a 24 16.4 cm eld. This system has an array of pixelated lutetium yttrium orthosilicate (LYSO) crystals (2 2 13mm3) and an array of 5-cm square position-sensitive photomultiplier tubes (PS-PMT). Coincidence detection is used

Figure 1 PEM camera. Image courtesy of Naviscan. (Color version of gure is available online.)

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Figure 2 (A) Patient undergoing PEM-guided biopsy. (B) PEM-positive lesion seen (red oval). (C) Positron-emitting needle approaches lesion for biopsy (red oval). (D) PEM-positive lesion is absent indicating successful biopsy (red oval). (E) Biopsy tissue is scanned to conrm accurate localization of lesion (red oval). Images courtesy of Naviscan. (Color version of gure is available online.)

ibility with MRI and the prospective ability to create a dedicated breast PET-MRI system that would incorporate all the benets of both modalities.18 See Table 1 for a summary and comparison of the well-dened PEM cameras.

Clinical Utility
The PEM system can identify disease when mammography or MRI is nondiagnostic, and multifocal disease not detected by other modalities, thereby altering patient man-

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Figure 3 Spatial resolution of Clear-PEM (A) without depth of interaction (DOI) and (B) with DOI. Images courtesy of Dr Jorge Neves. (Color version of gure is available online.)

agement (Figs. 5 and 6).11 In patients with known breast cancer, PEM and MRI were both reported to have an index lesion sensitivity of 93%, although there was an average of 11 days between biopsy and imaging, which could have been responsible for the FDG uptake and/or MRI enhancement. For unsuspected ipsilateral lesions or multifocal lesions, MRI had a near signicant superior sensitivity of 98% as opposed to PEM with a sensitivity of 85% (P 0.07)19; however, in a multicenter trial of patients with known breast cancer, there was an additive value of PEM, as PEM and MRI had an ipsilateral cancer detection of 74% versus 60% detection with MRI alone (P 0.001).20 These studies support the clinical value of PEM in patients with known breast cancer in identifying additional lesions. Further study is needed to evaluate

PEM assessment of mammographically suspicious lesions in patients unable to tolerate MRI.

Breast-Specic Gamma Cameras

Instrumentation
Standard gamma camera imaging with MIBI for breast cancer detection in the dense breast is limited by unacceptable sensitivity and negative predictive value21 because of resolution constraints. Dedicated BSG systems were developed to enhance resolution. The Dilon 6800 Gamma Camera (Dilon Technologies, Newport News, VA; Fig. 7) is approved by the FDA and referred to as BSGI. This camera has a dual head pixelated array of sodium iodide (NaI) crystals: 3 mm2 in a 64 48 matrix resulting in a 6 8-inch active area for imaging. This is accompanied by an array of 1-inch2 PSPMTs. A low-energy general-purpose collimator is used for imaging and a 15 slant-hole collimator can be used to image lesions near the chest wall.22 This system has an intrinsic resolution of 3.3-4.7 mm and an extrinsic spatial resolution of 6 mm at 3 cm distance from camera, and the drop-off in resolution with distance may be due to the collimator.23 Stereotactic biopsy guidance capability is available with this camera, and a pair of 20 slant hole collimators assist in localizing the lesion in the z axis (Fig. 8). GE received clearance recently from the FDA for a molecular breast imaging (MBI) camera, the Discovery NM 750b (GE), and this will soon be available commercially. This system uses CZT crystals and semiconductor photoelements as opposed to PMTs. A prototype for this system contains an 80 80 array of CZT crystals with a pixel size of 2.5 2.5 mm with a total detector

Figure 4 Clear-PEM Sonic prototype. Image courtesy of Dr Jorge Neves. (Color version of gure is available online.)

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Table 1 Parameters for PEM Imaging Devices Crystal Architecture: Pixel Size, mm

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Camera PEM-Flex II Clear-PEM Peng and Levin16 Vandenbroucke et al17

Crystal

Light Detection

Coincidence Intrinsic Time Resolution, Depth of Resolution, ns mm Interaction 3 5.2 8 3 2.4 1.3 1.0 0.837 N Y Y Y

LYSO Pixelated: 2 2 13 PS-PMT LYSO: Ce Pixelated: 2 2 20 APD CZT Pixelated: 40 40 5 Cross-strip electrode LYSO 3D-pixelated: 0.91 0.91 1 PS-APD

APD, avalanche photo diode; CZT, cadmium zinc telluride; LYSO, lutetium yttrium orthosilicate; PEM, positron emission mammography; PMT, photomultiplier tube; PS, position-sensitive.

area of 20 20 cm.24 In a similar system, this CZT conguration had 6.5% energy resolution at 140 keV, the intrinsic resolution was 2.5 mm, and the extrinsic resolution was 3.5 mm at 3 cm distance from the camera.25 When small pixels are used in a camera, there is a decrease in light collection and increased pixel crosstalk, and choice of collimation has a major effect on system resolution. Different crystals and camera architectures are under investigation to further improve resolution. Pixelated 2.05 2.05 5mm3 thallium-doped cesium iodide CsI(Tl) crystals integrated with thin tungsten collimators between the crystals coupled with PS-PMTs achieved a resolution to 3 mm at 3 cm distance from the camera when software methods were applied.26 LaBr3:Ce has a high scintillation yield, superior energy resolution at 140 keV,

and shorter attenuation length compared with NaI(Tl). Scintillator volume can be reduced by 25%, with the ability to improve intrinsic spatial resolution.27 A camera with a continuous LaBr3:Ce crystal block uses PS-PMTs, has both parallel and pinhole collimators, and the pinhole collimator is on a rotating arm to enable visualization of lesions close to the chest wall.28 A trapezoidal architecture (45 angle at the edges) with a monolithic thallium-doped cesium-iodide (CsI(Tl)) crystal successfully reduced edge effect and expanded the eld of view.29 Work is ongoing to determine the optimal crystal and camera architecture so that extrinsic resolution can be maximized and the smallest of breast lesions can be visualized. See Table 2 for a summary and comparison of the well-dened BSG cameras.

Figure 5 (A) After positive mammography, MRI revealed 3 foci that were highly suspicious for malignancy (red arrows). (B) PEM ndings implicated a fourth focus of malignancy (yellow circle). (C) Gross pathologic specimen: 4 foci of inltrating ductal carcinoma (3 black arrows, yellow circle). (D) Microscopic pathology of lesion seen only on PEM shows inltrating ductal carcinoma. Images courtesy of James Rogers, MD, Swedish Cancer Center, Seattle, WA, and Naviscan.

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Figure 6 Patient with MRI that was nondiagnostic because of cystic breasts. PEM images show heterogeneous uptake within the lower outer quadrant (yellow oval), and this was positive for malignancy on biopsy and at surgery. Images courtesy Kathy Schilling, MD, Boca Raton Community Hospital, Boca Raton, FL, and Naviscan. (Color version of gure is available online.)

Clinical Utility
The studies of the Dilon cameras are retrospective, and show clinically relevant sensitivity and a high degree of change in clinical management based on imaging results. In patients at high risk for breast cancer, BSGI had an overall sensitivity of 96.4% and specicity of 59.5%.30 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 ndings.31 In another retrospective analysis of patients undergoing BSGI, 11% of patients with Breast Imaging-Reporting and Data System (BI-RADS)32 1, 2, or 3 had positive BSGI, and 17% of these were positive for malignancy (Table 3 for BI-RADS denitions). In addition, 86% of patient with BI-RADS 4 could have avoided biopsy completely because of negative BSGI. Among the patients with known malignancy, 12% had positive BSGI at a secondary site and 50% of these were malignant. Overall, clinical management was changed signicantly in 14.2%, with another 6.3% in whom a negative BSGI could have prevented a biopsy.33 Mammographic and BSG images in a patient with dense breasts are shown in Fig. 9.

Figure 7 Breast-specic gamma camera simulating a MLO view. Image courtesy of Dilon Technologies. (Color version of gure is available online.)

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Figure 8 (A) Stereotactic gamma localization procedure with core needle biopsy apparatus. Image courtesy of Dilon Technologies. (B) Right view and (C) left view 20 slant-hole collimators assist in localization of lesion in the z axis. Images adapted from and courtesy of Dilon Technologies. (Color version of gure is available online.) Table 2 Parameters for BSG Imaging Devices Camera Dilon 6800 GE Discovery NM750b Trinci et al26 Crystal NaI CZT CsI(Tl) Crystal Architecture: Pixel Size, mm Pixelated: 3 3 Pixelated: 2.5 2.5 Pixelated: 2.05 2.05 Light Detection PS-PMT Semiconductor PS-PMT Extrinsic Resolution at 3 cm, mm 6 3.5 3

BSG, breast-specic gamma; CsI(Tl), thallium-doped cesium iodide; CZT, cadmium zinc telluride; NaI, sodium iodide; PMT, photomultiplier tube; PS, position-sensitive.

Table 3 Breast-Specic Gamma Camera Interpretation Recommendations 1. Homogeneous uptake of the radio-pharmaceutical in the breast or axilla is consistent with a normal study. (BI-RADS 1: negative) 2. Patchy or diffusely increased radiopharmaceutical uptake in the breasts is usually a normal variant, especially when the distribution correlates with mammographic anatomy. (BI-RADS 2: benign) 3. Features suggestive of benign disease of the breast are diffuse or patchy uptake of mild to moderate intensity, often bilateral, with ill-dened boundaries. 4. Multiple patchy areas of uptake, mild to moderate intensity. (BI-RADS 3: probably benign) 5. Small focal areas of increased radiopharmaceutical uptake in the breast or axilla (in the absence of radiopharmaceutical inltration): equivocal result, consistent with malignancy, inammation, atypia, fat necrosis. (BI-RADS 4: suspicious) 6. Intensity of focal uptake in malignant lesions is highly variable. Moderate-to-intense focal uptake with well-delineated contours is consistent with malignancy. (BIRADS 5: highly suggestive of malignancy) 7. Focal increased uptake (1 or more foci) in the ipsilateral axilla, in the presence of a primary lesion is strongly suggestive of axillary lymph node metastatic involvement (in the absence of radiopharmaceutical inltration). 8. Masking of high-activity lesions in the breast can improve visualization of adjacent breast tissues. Masking can be performed by placing appropriately sized pieces of lead between the lesion and the detector. Both the masked and original images should be included in the nal display. 9. Sources of error a. Inltration of the radiopharmaceutical administered in an arm vein may cause false-positive uptake in the axillary lymph nodes. Imaging of the injection site is helpful in evaluating the presence and extent of dose inltration. This is particularly important if an unsuspected breast lesion is discovered on the same side as the injection. Motion of the breast relative to the detector will decrease the accuracy of the test. b. The sensitivity, specicity, and accuracy of this test depend upon several factors, including the size of the breast neoplasm being imaged. Although the sensitivity of this test for subcentimeter tumors is high, around 95%, as with all radiologic examinations sensitivity decreases with lesion size.
Adapted from SNM Guideline for Breast Scintigraphy with breast-specic gamma cameras version 1.0 June 4, 2010.34 BIRADS, Breast Imaging-Reporting and Data System.32

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Figure 9 (A) Craniocaudal (CC) and (B) mediolateral oblique (MLO) conventional mammography reveals dense breasts with broglandular changes. (C) Breast specic gamma imaging CC and MLO views reveal a left breast lesion, and biopsy showed a 3-mm ductal carcinoma. Images courtesy of West Houston Radiology and Dilon Technologies.

Researchers from the Mayo Clinic performed several prospective trials with patients by using prototypes of the CZT system, and a large prospective trial of asymptomatic women (936 evaluable patients) was undertaken. These women had heterogeneous or extremely dense breasts and additional risk factors for breast cancer and underwent mammography and MBI. Prevalent screening MBI showed equivalent specicity relative to incident screening mammography (93% vs 91%,

P 0.069), and diagnostic yield was superior for mammography and MBI together (10.7 per 1000) versus mammography alone (3.2 per 1000; P 0.016).8 With respect to a high-risk population, patients with BI-RADS 4 or 5 lesions 2 cm in size underwent MBI before scheduled biopsy, and 59% of patients had malignant lesions at biopsy. Overall, MBI detected 90% of cancers and 93% of cancers 5 mm. This level of detection is clinically relevant, however sensitivity of

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Table 4 Breast-Specic Gamma Camera Clinical Indications

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A. Patients with recently detected breast malignancy 1. Evaluating the extent of disease (initial staging) 2. Detecting multicentric, multi-focal, or bilateral disease 3. Assessing response to neoadjuvant chemotherapy 4. Breast scintigraphy is addressed in the ACRs Appropriateness Criteria Panel on Breast Imaging35 B. Patients at high risk for breast malignancy 1. Suspected recurrence 2. Limited mammogram or previous malignancy was occult on mammogram C. Patients with indeterminate breast abnormalities and remaining diagnostic concerns 1. Nipple discharge with abnormal mammogram and/or sonographic abnormality with or without contrast ductography 2. Bloody nipple discharge with normal mammogram and/or ductogram 3. Signicant nipple discharge with unsuccessful ductogram 4. Evaluation of lesions when patient reassurance is warranted (BI-RADS 3) 5. Evaluation of lesions identied by other breast imaging techniques, palpable or non-palpable 6. Evaluation of palpable abnormalities not demonstrated by mammography or ultra-sound 7. Evaluation of multiple masses demonstrated on breast imaging 8. To aid in biopsy targeting 9. Evaluation of diffuse or multiple clusters of microcalcications 10. Evaluation of breasts for occult disease in cases of axillary lymph node metastases with unknown primary 11. Unexplained architectural distortion 12. Evaluation of suspicious mammographic nding seen on one view only 13. Evaluation of enhancing areas seen on MRI to increase specicity D. Patients with technically difcult breast imaging 1. Radiodense breast tissue 2. Implants, free silicone, or parafn injections compromising the mammogram E. Patients for whom Breast MRI would be indicated 1. MRI is diagnostically indicated, but not possible a. implanted pacemakers or pumps b. ferromagnetic surgical implants c. risk of nephrogenic systemic brosis response to gadolinium. d. body habitus exceeding the inside of the MRI bore e. patients with breasts too large to be evaluated within the breast coil f. patients with acute claustrophobia g. other factors limiting compliance with a prescribed MRI study. 2. As an alternative for patients who meet MRI screening criteria: BRCA1, BRCA2 mutations; parent, sibling, or child BRCA ; Lifetime risk of 20%-25% established; chest radiation between ages 10 and 30 F. Monitor neoadjuvant tumor response in patients undergoing preoperative chemotherapy 1. Determine the impact of therapy 2. Surgical planning for residual disease
Adapted from SNM Guideline for Breast Scintigraphy with breast-specic gamma cameras version 1.0 June 4, 2010.34 BIRADS, Breast Imaging-Reporting and Data System32; MRI, magnetic resonance imaging.

tumors 5 mm in diameter was 67%.24 To navigate patient selection and interpretation of this new modality, the Society of Nuclear Medicine has issued guidelines for BSG camera image interpretation recommendations and clinical indications, and these are presented in Tables 3 and 4, respectively.34,35

SLN and Radio Seed Localization

The physical features of intraoperative probe and camera design are described by Zanzonico and Heller (in this issue); however, their interaction with new surgical techniques is described here. The SLN method is now an essential imaging and surgical technique to evaluate the axilla for metastases while sparing many patients upper

extremity side effects in selected women. In conjunction with pathologic thin sections and special stains, the SLN procedure is as accurate in staging the axilla as axillary lymph node dissection.36,37 A variety of breast injection practices are advocated, and either ltered or unltered 99mTc-sulfur colloid is used before imaging. Some centers do not perform imaging before surgery; however, this is associated with excess upper extremity morbidity,38 and successful localization an SLN is inuenced by patient body mass index, institutional experience, and a positive imaging study.39 Vital blue dye is typically injected around the tumor bed in the operating room, and the search for SLNs begins: an SLN can be hot or blue or hot and blue (Fig. 10), and the rst 3 should be removed, after which the yield for increased accuracy is low.40 A new axillary reverse mapping (ARM) technique uses blue dye to distin-

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literature by van der Ploeg et al,43 14% of patients had sentinel node visualization on SPECT/CT only. Three-dimensional fusion imaging may be more helpful to surgical planning than planar imaging and/or skin marking (Fig. 11). It is conceivable SPECT/CT Digital Imaging and Communications in Medicine (ie, DICOM)44 images could also be used within a robotic surgery system to direct a surgical procedure and minimize upper extremity lymphatic damage. Gamma probes can also be used to locate nonpalpable breast cancers with the use of radiolabeled seeds, which can be placed during a biopsy procedure. A signicantly higher percentage of patients undergoing radio seed localization (RSL) achieved negative margins as opposed to those undergoing wire localization procedures,45,46 and the RSL can be performed as the same surgical setting as the SLN procedure. If there is enough 125iodine activity with a photopeak of 27 keV to overcome the down scatter of the 99mTc 140 keV photons, then both photopeaks can be detected easily at surgery.47 RSL is also effective when placed in the breast before neoadjuvant chemotherapy, as posttherapy lesions can be difcult to localize surgically. In this setting, a high percentage of negative margins was achieved,48 and further study is necessary to determine RSL usefulness within the malignant axilla before neoadjuvant chemotherapy.49

90Yttrium
90Yttrium

Microspheres

Figure 10 Radioactive hot and blue axillary sentinel lymph node in a patient with breast cancer (A) in vivo and (B) ex vivo with probe. Images courtesy of Dr Ronald Kaleya.

guish lymphatics draining the arm and sulfur colloid to identify lymph nodes draining the breast, and ARM lymphatics were avoided when possible at surgery. At 6-month follow-up, there were no cases of lymphedema when ARM lymphatics were preserved at surgery.41 With development of other types of dyes, some of the obstacles of differentiating ARM lymphatics versus SLNs could be overcome. In the forefront of technology is a high-resolution intraoperative gamma camera that communicates with a robotic arm to perform computer-assisted radioguided surgery.42 SPECT/CT is now widely available and can show the exact anatomical location of SLNs. It is helpful when the sentinel nodes are not detected by planar imaging or atypical in location, such as axillary level II, level III, supraclavicular or internal mammary. In a review of the

microspheres can effectively treat primary and metastatic liver disease and have shown usefulness in metastatic breast cancer. Because the liver has a dual blood supply, normal liver extracts 90% of oxygen from the portal vein, whereas the hepatic artery provides nutrients and oxygen to primary and most metastatic tumors. Although normal liver is highly tolerant to ischemia and has the ability to regenerate, patients with metastatic breast cancer have lower tolerance because of heavy pretreatment with hepatotoxic chemotherapies. 90Y (T 2.67 days, emitter) microspheres (YMS; Fig. 12) are administered via the hepatic artery in an interventional radiology suite. Two products are available and both are biocompatible but not biodegradable. SIR-Spheres (Sirtex) are composed of resin, contain 40-70 Becquerels (Bq) per sphere and are approximately 32 m in diameter. They are approved by the FDA for the treatment of colorectal cancer metastasized in the liver. TheraSpheres (MDS Nordion) are composed of glass, contain 2400-2700 Bq per sphere, are 20-30 m in diameter, and are approved by the FDA under the Humanitarian Device Exemption Guidelines for the treatment of unresectable hepatocellular carcinoma. Both products require a planning angiogram with eradication of nearby arteries to vital structures to avoid radiation damage after YMS therapy. 99mTc-macro-aggregated albumin (MAA) is infused into the hepatic artery at this time, images are acquired and quantitation of lung shunt is performed, and patients with excess lung activity have either

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Figure 11 SPECT/CT of left breast sentinel lymph node study showing (A) level 1 axillary lymph node and (B) retroclavicular sentinel lymph node.

reduced or no therapy (Fig. 13). YMS can be safely administered to patients with breast cancer and liver metastases,50-52 and tumor response on PET imaging was seen in 61%-63% of patients50,52 and in 95% of patients in a study by Coldwell et al51 (Fig. 14). Patients with response sus-

Figure 12 90Yttrium microspheres: each sphere is approximately 32 m in diameter. Illustration of electron micrograph courtesy of Sirtex.

Figure 13 Patient with breast cancer and hepatic metastases: (A) Anterior planar image after 99mTc-MAA was injected into the common hepatic artery during planning angiogram. MAA activity is seen heterogeneously within the right and left hepatic lobes and there is no signicant hepatic lung shunt. Free pertechnetate is noted in the thyroid and urine. (B) After intrahepatic arterial therapy of the right hepatic lobe with 90yttrium microspheres, bremsstrahlung images conrm localization of the spheres. Images courtesy of Dr Michael Cohn.

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Figure 14 Patient with breast cancer and hepatic metastases: coronal fused FDG-PET images (A) before therapy and (B) 6-months after therapy with 90yttrium microspheres showing signicant treatment response. Images courtesy of Dr Michael Cohn.

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