High-resolution Positron Emission Mammography Research Articles

Development of a mechatronic guidance system for targeted ultrasound-guided biopsy under high-resolution positron emission mammography localization.

Image-guided needle biopsy of small, detectable lesions is crucial for early-stage diagnosis, treatment planning, and management of breast cancer. High-resolution positron emission mammography (PEM) is a dedicated functional imaging modality that can detect breast cancer independent of breast tissue density, but anatomical context and real-time needle visualization are not yet available to guide biopsy. We propose a mechatronic guidance system integrating an ultrasound (US)-guided core-needle biopsy (CNB) with high-resolution PEM localization to improve the spatial sampling of breast lesions. This paper presents the benchtop testing and phantom studies to evaluate the accuracy of the system and its constituent components for targeted PEM-US-guided biopsy under simulated high-resolution PEM localization. A mechatronic guidance system was developed to operate with the Radialis PEM system and a conventional US system. The system includes a user-operated guidance arm and end-effector biopsy device, integrating a US transducer and CNB gun, with its needle focused on a remote center of motion (RCM). Custom software modules were developed to track, display, and guide the end-effector biopsy device. Registration of the mechatronic guidance system to a simulated PEM detector plate was performed using a landmark-based method. Testing was performed with fiducials positioned in the peripheral and central regions of the simulated detector plate and registration error was quantified. Breast phantom experiments were performed under ideal detection and localization to evaluate for bias in the end-effector biopsy device. The accuracy of the complete mechatronic guidance system to perform targeted breast biopsy was assessed using breast phantoms with simulated lesions. Three-dimensional positioning error was quantified, and principal component analysis assessed for directional trends in 3D space within 95% prediction intervals. Targeted breast biopsies with test phantoms were performed and an overall in-plane needle targeting error was quantified. The mean registration errors were 0.63mm (N=44) and 0.73mm (N=72) in the peripheral and central regions of the simulated PEM detector plate, respectively. A 3D 95% prediction ellipsoid shows an error volume <2.0mm in diameter, centered on the mean registration error. Under ideal detection and localization, targets <1.0mm in diameter can be sampled with 95% confidence. The complete mechatronic guidance system was able to successfully spatially sample simulated breast lesions, 4mm and 6mm in diameter and height (N=20) in known 3D positions in the PEM image coordinate space. The 3D positioning error was 0.85mm (N=20) with 0.64mm in-plane and 0.44mm cross-plane component errors. Targeted breast biopsies resulted in a mean in-plane needle targeting error of 1.08mm (N=15) allowing for targets 1.32mm in radius to be sampled with 95% confidence. We demonstrated the utility of our mechatronic guidance system for targeted breast biopsy under high-resolution PEM localization. Breast phantom studies showed the ability to accurately guide, position, and target breast lesions with the accuracy to spatially sample targets <3.0mm in diameter with 95% confidence. Future work will integrate the developed system with the Radialis PEM system toward combined PEM-US-guided breast biopsy.

Development of an angled Si-PM-based detector unit for positron emission mammography (PEM) system

Positron emission mammography (PEM) systems have higher sensitivity than clinical whole body PET systems because they have a smaller ring diameter. However, the spatial resolution of PEM systems is not high enough to detect early stage breast cancer. To solve this problem, we developed a silicon photomultiplier (Si-PM) based detector unit for the development of a PEM system. Since a Si-PM's channel is small, Si-PM can resolve small scintillator pixels to improve the spatial resolution. Also Si-PM based detectors have inherently high timing resolution and are able to reduce the random coincidence events by reducing the time window. We used 1.5×1.9×15mm LGSO scintillation pixels and arranged them in an 8×24 matrix to form scintillator blocks. Four scintillator blocks were optically coupled to Si-PM arrays with an angled light guide to form a detector unit. Since the light guide has angles of 5.625°, we can arrange 64 scintillator blocks in a nearly circular shape (a regular 64-sided polygon) using 16 detector units. We clearly resolved the pixels of the scintillator blocks in a 2-dimensional position histogram where the averages of the peak-to-valley ratios (P/Vs) were 3.7±0.3 and 5.7±0.8 in the transverse and axial directions, respectively. The average energy resolution was 14.2±2.1% full-width at half-maximum (FWHM). By including the temperature dependent gain control electronics, the photo-peak channel shifts were controlled within ±1.5% with the temperature from 23°C to 28°C. With these results, in addition to the potential high timing performance of Si-PM based detectors, our developed detector unit is promising for the development of a high-resolution PEM system.

Abstract P1-02-12: High-resolution specimen-positron emission mammography (s-PEM) indicates the spread of cancer in breast-conserving surgery

Abstract Background: Breast cancer surgery, including breast-conserving surgery or sentinel lymphnode biopsy, has become minimally invasive. Recent consensus guidelines on the margins for breast-conserving surgery have defined a negative margin as one with no ink on tumor, regardless of the distance from the tumor, whereas a positive margin has ink on the tumor. Therefore, the extent of required tumor resection will decrease for cosmoses and expand the indications for breast-conserving surgery. Therefore, there is a real need for a more accurate imaging of tumor spread. In particular, a functional imaging of breast cancer specimens will help determine negative margins in breast-conserving surgery. We collaborated with Sendai Medical Imaging Center (SMIC) who have high-resolution positron emission mammography (PEM) with the novel scintillator Pr3+-doped transparent ceramic Lu3Al5O12 (Pr:LuAG) for the imaging of breast cancer specimen with 18F-fluodeoxyglucose (FDG). Methods: With the approval of the hospital ethics committee, positron emission tomography (PET) was conducted preoperatively on the day of surgery with 18F-FDG. After the PET results were explained to the patients, breast-conserving surgery was performed in 11 patients from February to July 2014. In the operating room, medical staff exposures were calculated with a portable dosimeter. All of the cases were carried out intraoperative frozen sections that were taken from all sides of the outside of the specimens. The specimens were serially sectioned in 5-mm slices for permanent histology. After the specimens were removed, they were sent to the SMIC and high-resolution specimen-PEM (s-PEM) was conducted. We evaluated the detection rate of s-PEM in in situ or invasive lesions (extent of locations were tolerated up to a 10% error), the predictive value of margin status between s-PEM and frozen section analysis and medical stuff exposure. Results: In 11 breast specimens, eight invasive lesions and 15 in situ lesions (excluding the foci that exist in less than three carcinoma ducts) were confirmed by permanent histology. s-PEM detected all of the invasive lesions and 14 out of 15 in situ lesions. Three breast specimens had positive margins in permanent histology. Two out of three cases with positive margin accumulated 18F-FDG at the edge of the specimens, which were considered positive margins with s-PEM, whereas positive margins were only one out of three of the frozen section analysis. In contrast, a false positive margin was found in only one case with s-PEM, which confirmed the preoperative core-needle biopsy that was diagnosed as an intraductal proliferative lesion. Medical staff exposure was determined for the operator, first assistant, second assistant, anesthesiologist, scrab nurse and circulating nurse as 31, 34, 25, 11, 21 and 6 µSV, respectively. Conclusion: s-PEM detected not only invasive lesions but also in situ lesions with great accuracy. It might accelerate the decrease in the extent of resection required in breast-conserving surgery. However, further studies are needed to elucidate the characteristics of the false positive cases in s-PEM. Citation Format: Gou Watanabe, Masatoshi Itoh, Dan Kyokutou, Mika Watanabe, Takanori Ishida, Akihiko Suzuki, Minoru Miyashita, Hiroshi Tada, Naoko Mori, Noriaki Ohuchi. High-resolution specimen-positron emission mammography (s-PEM) indicates the spread of cancer in breast-conserving surgery [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-12.

Simulation and evaluation of a high resolution VIP PEM system with a dedicated LM-OSEM algorithm

Over the last two decades there have been a growing number of designs for positron emission tomography (PET) cameras optimized to image the breast. These devices, commonly known as positron emission mammography (PEM) cameras allow much more spatial resolution by putting the photon detectors directly on the breast. PEM cameras have a compact geometry with a restricted field of view (FOV)thus exhibiting higher performance and lower cost than large whole body PET scanners. Typical PEM designs are based on scintillators such as bismuth germanate (BGO), lutetium oxorthosilicate (LSO) orlutetium yttrium orthosicilate (LYSO), and characterized by large parallax error due to deficiency of thedepth of interaction (DOI) information from crystals. In the case of parallel geometry PEM,large parallax error results in poor image resolution along the vertical axis.In the framework of the Voxel Imaging PET (VIP) pathfinder project,we propose a high resolution PEM scanner based on pixelated solid-state CdTe detectors. The pixel PEM device with a millimeter-size pixel pitch provides an excellent spatial resolution inall directions 8 times better than standard commercial devices with a point spread function (PSF) of 1 mm full width at halfmaximum (FWHM) and excellent energy resolution of down to 1.6% FWHM at 511 keV photons at room temperature. The system is capable to detect down to 1 mm diameter hot spheres in warm background.

The System Design, Engineering Architecture, and Preliminary Results of a Lower-Cost High-Sensitivity High-Resolution Positron Emission Mammography Camera

A lower-cost high-sensitivity high-resolution positron emission mammography (PEM) camera is developed. It consists of two detector modules with the planar detector bank of 20 × 12 cm(2). Each bank has 60 low-cost PMT-Quadrant-Sharing (PQS) LYSO blocks arranged in a 10 × 6 array with two types of geometries. One is the symmetric 19.36 × 19.36 mm(2) block made of 1.5 × 1.5 × 10 mm(3) crystals in a 12 × 12 array. The other is the 19.36 × 26.05 mm(2) asymmetric block made of 1.5 × 1.9 × 10 mm(3) crystals in 12 × 13 array. One row (10) of the elongated blocks are used along one side of the bank to reclaim the half empty PMT photocathode in the regular PQS design to reduce the dead area at the edge of the module. The bank has a high overall crystal packing fraction of 88%, which results in a very high sensitivity. Mechanical design and electronics have been developed for low-cost, compactness, and stability purposes. Each module has four Anger-HYPER decoding electronics that can handle a count-rate of 3 Mcps for single events. A simple two-module coincidence board with a hardware delay window for random coincidences has been developed with an adjustable window of 6 to 15 ns. Some of the performance parameters have been studied by preliminary tests and Monte Carlo simulations, including the crystal decoding map and the 17% energy resolution of the detectors, the point source sensitivity of 11.5% with 50 mm bank-to-bank distance, the 1.2 mm-spatial resolutions, 42 kcps peak Noise Equivalent Count Rate at 7.0-mCi total activity in human body, and the resolution phantom images. Those results show that the design goal of building a lower-cost, high-sensitivity, high-resolution PEM detector is achieved.

Characterization of avalanche photodiode arrays for the ClearPEM and ClearPEM-Sonic scanners

The ClearPEM scanner is a high-resolution Positron Emission Mammography prototype, developed by the Portuguese PET Consortium in the framework of the Crystal Clear Collaboration at the European Organization for Nuclear Research (CERN). The scanner is based on a novel readout scheme which uses fine-pitch scintillator crystals, avalanche photodiodes, low-noise high-gain integrated electronics and a fast reconfigurable digital data acquisition system. The scanner uses two planar detector heads each composed of 96 detector modules. The detector module is composed of a matrix of 32 identical 2 × 2 × 20 mm3 LYSO:Ce scintillator crystals, coupled at both ends to Hamamatsu S8550 APD arrays for Depth-of-Interaction (DOI) measurements. More recently, a new scanner named ClearPEM-Sonic which combines the ClearPEM technology with an Ultrasound apparatus, is being produced. A set of 984 APD arrays used in both scanner assemblies followed a quality control protocol and a characterization procedure. This paper describes the methods used in these measurements and the results obtained with the full APD production batch.

Applications for positron emission mammography

High resolution positron emission mammography (PEM) can address the current clinical needs of breast cancer patients and the requirements for future translational work. Combining the quantitative capabilities of positron emission tomography (PET) with millimeter resolution, PEM can image the earliest in situ forms of breast cancer as well as putative cancer precursor lesions (e.g., atypical ductal hyperplasia) whose behavior is important for prevention studies. The importance of the ability to detect intraductal cancer cannot be overemphasized, for several reasons: at least one-third of new cancers are detected at this intraductal stage, intervention at this stage represents the best opportunity for complete cure, and a significant number of invasive cancers contain an intraductal component. Without knowledge of the extent of the intraductal component, surgeons are unable to completely excise cancers about a third of the time, leading to unnecessary re-excisions or radiation therapy. Current investigations aimed at specifying best practices in radiotherapy of DCIS patients are stymied by the lack of objective quantitative methods of rapidly assessing response. Other future applications of PEM are suggested, including an information technology project built on PEM that promises to individualize therapy and facilitate surveillance of high risk populations. The high overall accuracy of PEM (i.e., both specificity and sensitivity) is an unusual and welcome development in the history of breast imaging. With this high accuracy, and continued technical innovation to reduce radiation dose, PEM may someday replace X-ray mammography as a first line approach to breast cancer detection.

Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer

Background High-resolution positron-emission mammography (PEM) is a new device, which allows the imaging of breast tissue. A prospective study was performed to assess the accuracy of PEM in newly diagnosed breast cancer patients. Methods In a prospective multicenter study, 44 women with confirmed breast cancers were imaged with a high-resolution PEM scanner (Naviscan PET Systems, Rockville, MD) with 18F-fluorodeoxyglucose. The images were blindly evaluated and were compared with final pathology. Results The majority of the index lesions were seen on PEM (89%, 39/44). PEM detected 4 of 5 incidental breast cancers, 3 of which were not seen by any other imaging modalities. Of 19 patients undergoing breast-conserving surgery, PEM correctly predicted 6 of 8 (75%) patients with positive margins and 100% (11/11) with negative margins. Conclusion The current PEM device shows promise in detecting breast malignancies and may assist in the planning of adequate partial mastectomy procedures to better ensure negative margins.

A prototype modular detector design for high resolution positron emission mammography imaging

Current challenges facing us in developing dedicated position emission tomography (PET) system for metabolic breast mammography (PEM) and small animal (ANIPET) are to achieve high spatial resolution (less than 2 mm) and high efficiency. It is also crucial to extend the sensitive areas of PEM detectors to their periphery in order to overcome the difficulty in imaging near a patient's chest wall. This limitation of the periphery dead region was revealed in the clinical trials of our previously developed PEM-I system. In the new study, we developed prototype detectors by using position-sensitive photomultiplier tubes (PS-PMTs) and pixelated bismuth germanate (BGO) crystals with depth encoding scheme to detect and localize gamma rays. The procedures in crystal processing include cutting, polishing, encapsulating, separating, and re-gluing. We also developed front-end electronic circuits including high-voltage dividers, anode resistor chains, position readout circuits, and last dynode timing circuits. Methods for combining four PS-PMTs with simple X+, X-, Y+, Y- outputs have been developed to further simplify the position recording. The detectors were constructed in the structure of array (two in the system)-module (four in each array)-unit (four in each module). The basic unit of one crystal and one PS-PMT can be field replaceable. Our new prototype detectors show that the proposed PEM-II system has a spatial resolution of 1.8 mm (versus 2.8 mm in PEM-I), a timing resolution of 10.3 ns (versus 12 ns in PEM-I), and a field-of-view of 88 mm /spl times/ 88 mm (versus 64 mm /spl times/ 56 mm in PEM-I). Compared with our previous PEM-I system, it demonstrates that the design improves the spatial resolution, enhances the detector field-of-view, and significantly reduces the peripheral dead regions.