Phantom evaluations of a dedicated dual-head scintimammography system

Results of aboratory evaluations are presented of the dual-head scintimammography system using two opposed and co-registered compact gamma heads. The system is intended for clinical studies imaging suspicious lesions in a compressed breast. The studies were performed using 5 cm and 6 cm compressed breast phantoms with lesion sizes from 6 to 10 mm and lesion to breast tissue activity ratios from 6 to 10. Two imagers with a field-of-view (FOV) of 15 cm×20 cm were placed on the opposite sides of the breast phartoms. In some studies anthropomorphic torso phantom was used to simulate realistic scatter gamma radiation field. Two types of parallel-hole lead collimators were employed. Combining the co-registered images from both detector heads resulted in an over two-fold increase in lesioin contrast in the central plane of the phantom and substantially increased detection sensitivity over the whole breast volume, especially of asymmetrically placed small lesions. The results confirm the important advantage of a co-registoed two-head scintimammography system over a single head system in lesion detection and localization.     

Principles of nuclear medicine imaging: planar, SPECT, PET, multi-modality, and autoradiography systems

The underlying principles of nuclear medicine imaging involve the use of unsealed sources of radioactivity in the form of radiopharmaceuticals. The ionizing radiations that accompany the decay of the administered radioactivity can be quantitatively detected, measured, and imaged in vivo with instruments such as gamma cameras. This paper reviews the design and operating principles, as well as the capabilities and limitations, of instruments used clinically and preclinically for in vivo radionuclide imaging. These include gamma cameras, single-photon emission computed tomography (SPECT) scanners, and positron emission tomography (PET) scanners. The technical basis of autoradiography is reviewed as well.     

Detecting infiltrating lobular carcinoma using scintimammographic breast specific gamma imaging

This study evaluated the effectiveness of scintimammography performed with gamma cameras optimized for breast imaging in the detection of infiltrating lobular carcinoma. This new procedure, Breast Specific Gamma Imaging (BSGI), was conducted on 105 patient presenting with 113 breast lesions. Studies were conducted at two medical centers using three prototype cameras [14, 16]. Biopsy and pathology reports were obtained for all cases and, of the 34 detected carcinomas, 6 were determined to be infiltrating lobular type without mixed component other than lobular carcinoma in situ. Of the 6 lesions, 4 were smaller than 1 cm, the smallest moasuring 3 mm at biopsy. BSGI detected all 6 of the lobular carcinomas and correctly identified the secondary lesion in the only multifocal case. The BSGI foci sizes matched the lesion size at biopsy to within +/-5.5 mm, with about an equal number of cases ovar and under estimated. Conclusion: BSGI provides an effective tool for the detection of lobular carcinoma and in the determination of lesion size and multifocality.     

Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia

Intranasal instillation techniques are used to deliver various substances to the upper and lower respiratory tract (URT and LRT) in mice. Here, we quantify the relative distribution achieved with intranasal delivery of a nonabsorbable tracer, (99m)Tc-labeled sulfide-colloid. Relative distribution was determined by killing mice after instillation and quantifying the radioactivity in dissected tissues using gamma scintigraphy. A significant effect of delivery volume on relative distribution was observed when animals were killed 5 min after instillation delivered under gas anesthesia. With a delivery volume of 5 microl, no radiation was detected in the LRT; this increased to a maximum of 55.7 +/- 2.5% distribution to the LRT when 50 microl were delivered. The majority of radiation not detected in the LRT was found in the URT. Over the course of the following 1 h, radiation in the LRT remained constant, while that in the URT decreased and appeared in the gastrointestinal tract. Instillation of 25 microl into anesthetized mice resulted in 30.1 +/- 6.9% distribution to the LRT, while only 5.3 +/- 1.5% (P < 0.05) of the same volume was detected in the LRT of awake mice. Varying the body position of mice did not affect relative distribution. When using intranasal instillation, the relative distribution between the URT and LRT and the gastrointestinal tract is heavily influenced by delivery volume and level of anesthesia.     

Investigation of the dose distribution for a cone beam CT system dedicated to breast imaging

Cone-beam breast Computed Tomography (bCT) is an X-ray imaging technique for breast cancer diagnosis, in principle capable of delivering a much more homogeneous dose spatial pattern to the breast volume than conventional mammography, at dose levels comparable to two-view mammography. We present an investigation of the three-dimensional dose distribution for a cone-beam CT system dedicated to breast imaging. We employed Monte Carlo simulations for estimating the dose deposited within a breast phantom having a hemiellipsoidal shape placed on a cylinder of 3.5 cm thickness that simulates the chest wall. This phantom represents a pendulant breast in a bCT exam with the average diameter at chest wall, assumed to correspond to a 5-cm-thick compressed breast in mammography. The phantom is irradiated in a circular orbit with an X-ray cone beam selected from four different techniques: 50, 60, 70, and 80 kVp from a tube with tungsten anode, 1.8 mm Al inherent filtration and additional filtration of 0.2 mm Cu. Using the Monte Carlo code GEANT4 we simulated a system similar to the experimental apparatus available in our lab. Simulations were performed at a constant free-in-air air kerma at the isocenter (1 μGy); the corresponding total number of photon histories per scan was 288 million at 80 kVp. We found that the more energetic beams provide a more uniform dose distribution than at low energy: the 50 kVp beam presents a frequency distribution of absorbed dose values with a coefficient of variation almost double than that for the 80 kVp beam. This is confirmed by the analysis of the relative dose profiles along the radial (i.e. parallel to the “chest wall”) and longitudinal (i.e. from “chest wall” to “nipple”) directions. Maximum radial deviations are on the order of 25% for the 80 kVp beam, whereas for the 50 kVp beam variations around 43% were observed, with the lowest dose values being found along the central longitudinal axis of the phantom.     

Anatomical evaluation of CT-MRI combined femoral model

Background

Breast density is a significant breast cancer risk factor. Currently, there is no standard method for measuring this important factor. Work presented here represents an essential component of an ongoing project that seeks to determine the appropriate method for calibrating (standardizing) mammography image data to account for the x-ray image acquisition influences. Longer term goals of this project are to make accurate breast density measurements in support of risk studies.

Methods

Logarithmic response calibration curves and effective x-ray attenuation coefficients were measured from two full field digital mammography (FFDM) systems with breast tissue equivalent phantom imaging and compared. Normalization methods were studied to assess the possibility of reducing the amount of calibration data collection. The percent glandular calibration map functional form was investigated. Spatial variations in the calibration data were used to assess the uncertainty in the calibration application by applying error propagation analyses.

Results

Logarithmic response curves are well approximated as linear. Measured effective x-ray attenuation coefficients are characteristic quantities independent of the imaging system and are in agreement with those predicted numerically. Calibration data collection can be reduced by applying a simple normalization technique. The calibration map is well approximated as linear. Intrasystem calibration variation was on the order of four percent, which was approximately half of the intersystem variation.

Conclusion

FFDM systems provide a quantitative output, and the calibration quantities presented here may be used for data acquired on similar FFDM systems.     

Quantitative evaluation of transmission properties of breast tissue equivalent materials under Compton scatter imaging setup

To explore the potential of utilizing Compton scattered x-ray photons for imaging applications, it is critical to accurately evaluate scattered x-ray transmission properties of targeted tissue materials. In this study, scattered x-ray transmission of breast tissue equivalent phantoms was evaluated. Firstly, two validations were carried out using a primary x-ray beam at 80 kVp with both experimental measurement (ion chamber with narrow-beam setup) and analytical calculation (Spektr toolkit). The tungsten-anode x-ray spectrum model was thus validated by measuring and calculating the transmission through increasing thickness of 1100 Aluminum filters. Similarly, the composition models of breast tissue equivalent phantoms (CIRS, 012A) were validated by measuring and calculating x-ray transmission for three different breast compositions (BR30/70, BR50/50, and BR70/30). Following validation, transmission properties of Compton scattered x-ray photons were measured with a GOS based linear array detector at the 90° angle from the primary beam. The same study was performed through three independent approaches: experimental measurement, analytical calculation, and Monte Carlo simulation (GEANT4). For all three methods, the scattered x-ray photon transmission as functions of phantom thickness were determined and fit into exponential functions. The transmission curves from all three methods matched reasonably well, with a maximum difference of 6.3% for the estimated effective attenuation coefficients of the BR50/50 phantom. The relative difference among the three methods of estimated attenuation is under 3.5%. As an initial step to develop a novel Compton scatter-based breast imaging system, the quantitative results from this study paved a fundamental base for future work.     

Nonlinear Dual Reconstruction of SPECT Activity and Attenuation Images

In single photon emission computed tomography (SPECT), accurate attenuation maps are needed to perform essential attenuation compensation for high quality radioactivity estimation. Formulating the SPECT activity and attenuation reconstruction tasks as coupled signal estimation and system parameter identification problems, where the activity distribution and the attenuation parameter are treated as random variables with known prior statistics, we present a nonlinear dual reconstruction scheme based on the unscented Kalman filtering (UKF) principles. In this effort, the dynamic changes of the organ radioactivity distribution are described through state space evolution equations, while the photon-counting SPECT projection data are measured through the observation equations. Activity distribution is then estimated with sub-optimal fixed attenuation parameters, followed by attenuation map reconstruction given these activity estimates. Such coupled estimation processes are iteratively repeated as necessary until convergence. The results obtained from Monte Carlo simulated data, physical phantom, and real SPECT scans demonstrate the improved performance of the proposed method both from visual inspection of the images and a quantitative evaluation, compared to the widely used EM-ML algorithms. The dual estimation framework has the potential to be useful for estimating the attenuation map from emission data only and thus benefit the radioactivity reconstruction.     

Hot and cold contrasts in high-resolution Tc-99m planar scintigraphy: A survey of fifty-two camera heads using the PICKER thyroid phantom

This study was aimed at comparing the sensitivity and hot and cold contrasts obtained when imaging the PICKER thyroid phantom using gamma cameras fitted with either their ultra-high or high-resolution low-energy parallel hole collimator.Seventeen camera models from Elscint, General Electric, Siemens and Sopha Medical Vision were involved in the study for a total of 30 cameras and 52 camera heads. A single operator conducted the study in order to minimize the impact of human factors. The phantom contained about 74 MBq ^99mTc and was imaged at 10 cm from the collimator face with the energy window that are recommended by the camera manufacturer. A total of 1 million counts were accumulated.Hot and cold contrasts were in mean of about 0.05 higher when using an ultra-high-resolution than when using a high-resolution low-energy collimator. This higher contrast was obtained at the expense of a mean reduction in sensitivity of 30%. In particular, Elscint cameras demonstrated a 30% lower sensitivity whatever the collimator type. The Sopha Medical Vision DST and DSX cameras and the General Electric Magicam camera offered the lowest contrasts among the cameras with a high-resolution collimator. Although this was accompanied by a higher than the mean sensitivity for the DST and DSX, the Magicam demonstrated sensitivity roughly identical to the mean of all the cameras with a high-resolution collimator.     

Rhodopsin-enhanced GTPase activity of the inhibitory GTP-binding protein of adenylate cyclase

Work in several laboratories has shown that Gi, the inhibitory guanyl nucleotide-binding protein of the adenylate cyclase system, is similar in many ways to transducin, the guanyl nucleotide-binding protein of the retinal light-activated cGMP phosphodiesterase system. Separated subunits of purified transducin, T alpha (approximately 39 kDa) and T beta gamma (approximately 35 and approximately 10 kDa), do not exhibit GTPase activity; GTPase activity is observed when the subunits are combined in the presence of rhodopsin ( Fung , B. K.-K. (1983) J. Biol. Chem. 258, 10495-10502). Subunits of Gi, Gi alpha (approximately 41 kDa), and Gi beta gamma (approximately 35 and approximately 10 kDa) were prepared from rabbit liver membranes. It was found that Gi beta gamma could replace T beta gamma in reconstituting the rhodopsin-stimulated GTPase activity of T alpha. Gi alpha exhibited rhodopsin-stimulated GTPase activity when reconstituted with Gi beta gamma or T beta gamma. GTPase activity was a function of Gi alpha concentration when Gi beta gamma or T beta gamma was constant, and the GTPase activity of a given amount of Gi alpha was dependent on Gi beta gamma concentration. These studies demonstrate that the GTPase activity of Gi resides in Gi alpha and further establish that Gi alpha and Gi beta gamma are functionally analogous to T alpha and T beta gamma, respectively.     

Effect of glutamine on the degradation of glutamine synthetase in hepatoma tissue-culture cells.

In certain lines of hepatoma tissue-culture cells, the extracellular glutamine concentration regulates the specific activity of glutamine synthetase. By quantifying the radioactivity in immunoprecipitated glutamine synthetase on polyacrylamide gels, we found that the rate of degradation, but not of synthesis, of glutamine synthetase is a sensitive function of extracellular glutamine. The activiy that degrades this enzyme appears to be labile.     

MRI/PET nonrigid breast-image registration using skin fiducial markers

We propose a finite-element method (FEM) deformable breast model that does not require elastic breast data for nonrigid PET/MRI breast image registration. The model is applicable only if the stress conditions in the imaged breast are virtually the same in PET and MRI. Under these conditions, the observed intermodality displacements are solely due the imaging/reconstruction process. Similar stress conditions are assured by use of an MRI breast-antenna replica for breast support during PET, and use of the same positioning. The tetrahedral volume and triangular surface elements are used to construct the FEM mesh from the MRI image. Our model requires a number of fiducial skin markers (FSM) visible in PET and MRI. The displacement vectors of FSMs are measured followed by the dense displacement field estimation by first distributing the displacement, vectors linearly over the breast surface and then distributing them throughout the volume. Finally, the floating MRI image is warped to a fixed PET image, by using an appropriate shape function in the interpolation from mesh nodes to voxels. We tested our model on an elastic breast phantom with simulated internal lesions and on a small number of patients imaged, with FMS using PET and MRI. Using simulated lesions (in phantom) and real lesions (in patients) visible in both PET and MRI, we established that the target registration error (TRE) is below two pet voxels.     

La caméra à semi-conducteur D-Spect : aspects techniques et applications cliniques

Clinical practice in nuclear medicine has largely changed in the last decade, particularly with the arrival of PET/CT and SPECT/CT. New semiconductor cameras could represent the next evolution in our nuclear medicine practice. Due to the resolution and sensitivity improvement, this technology authorizes fast speed acquisitions, high contrast and resolution images performed with low activity injection. The dedicated cardiology D-Spect camera (Spectrum Dynamics, Israel) is based on semiconductor technology and provides an original system for collimation and images reconstruction. We describe here our clinical experience in using the D-Spect with a preliminary study comparing D-DPECT and conventional gamma camera.     

Antibody-based enrichment of peptides on magnetic beads for mass-spectrometry-based quantification of serum biomarkers

A major bottleneck for validation of new clinical diagnostics is the development of highly sensitive and specific assays for quantifying proteins. We previously described a method, stable isotope standards with capture by antipeptide antibodies, wherein a specific tryptic peptide is selected as a stoichiometric representative of the protein from which it is cleaved, is enriched from biological samples using immobilized antibodies, and is quantitated using mass spectrometry against a spiked internal standard to yield a measure of protein concentration. In this study, we optimized a magnetic-bead-based platform amenable to high-throughput peptide capture and demonstrated that antibody capture followed by mass spectrometry can achieve ion signal enhancements on the order of 10(3), with precision (CVs <10%) and accuracy (relative error approximately 20%) sufficient for quantifying biomarkers in the physiologically relevant ng/mL range. These methods are generally applicable to any protein or biological fluid of interest and hold great potential for providing a desperately needed bridging technology between biomarker discovery and clinical application.     

Evaluating flux of labeled albumin into the pulmonary interstitium of sheep lungs.

A noninvasive method was used to measure the movement of 131I-labeled albumin across the pulmonary microvascular barrier of a blood-perfused in situ sheep lung lymph preparation. After injection of labeled albumin into the blood, external measurements of gamma activity were taken for 2 h. The interstitial concentrations were calculated by applying the external activities and sampled lung lymph concentrations to a mass transport model. For the external activities and lymph activities to yield the same quantitative results, two modifications were necessary. First, lymph concentrations were corrected for transport delay from the lymphatic system. Second, externally detected radioactivity had to be corrected for the contribution of unbound nuclide. Application of a mathematical model to the data indicated the extravascular distribution volume for albumin was 79% of the pulmonary blood volume, and the extravascular distribution volume for radiolabeled iodide was 4.42 times greater than the pulmonary blood volume. The permeability-surface area product for iodide in the lung was estimated to be 0.274 ml.min-1.g blood-free dry lung wt-1. The transport delay in the lymphatic system was approximately 30-45 min and represented a volume of 1.44-2.80 ml.     

High-resolution gamma-camera for molecular breast imaging: First clinical results

Scintimair mography is a molecular breast imaging technique using tumour-seeking radiopharmaceuticals; with standard gamma-cameras, is proved of value especially when mammography is indeterminate and in women with dense breasts; nevertheless, this technique shows a high sensitivity only for cancers >1 cm. The issue of detecting small cancers is critical for the future development and clinical usefulness of breast imaging with radiopharmaceuticals, because other modalities are increasingly employed for early identification of small abnormalities. The use of high-resolution dedicated cameras for breast imaging is the best option to improve small cancers' detection: they allow greater flexibility in patient positioning, and the availability of projections similar to those of mammography. Moreover, the detector can be placed directly against the breast, and a mild compression is possible, with the results of reducing breast thickness, increasing the target-to-background ratio and the sensitivity. Our first clinical findings using the dedicased camera Lumagem 3200S (Gamma Medica, Inc., Northridge, USA) are very satisfactory. Till now, 29 patients with BI-RADS category III and IV lesions ≤1 cm were prospectively evaluated using a conventional gamma-camera and the dedicated device. Four out nine (44%) of the malignant lesions were detected with the standard gamma-camera, whereas the high-resolution camera visualized all the breast cancers. The standard gamma-camera and the dedicated one showed the same specificity: 19 out of 20 (95%) benign lesions were negative. Our results indicate that molecular breast imaging with this dedicated camera is able to detect small cancers in patients with probably benign or low-suspicion to indeterminate mammographic findings.     

Use of uniform shots for robust planning of mask-based treatment in Gamma Knife Icon

PurposeTo verify whether Icon automatic correction is robust in preserving plan quality.Materials/methodsAn end-to-end phantom was used to verify Icon’s correction accuracy qualitatively. For quantitative assessment, two plans, a composite- and a uniform-shot-only, were created for an elliptical- (E) and a sausage-shaped (S) lesion inside a PseudoPatient head phantom with a film insert. The phantom was irradiated in the planned and three other positions under each plan: 14° pitch (B); 14° rotation + 8° pitch (C); 95° rotation + 4-cm shift (D).ResultsIcon accurately corrects the locations of the shots. For the uniform-shot plans: all gamma index passing rates were >97%, and the differences between the planned and the delivery doses (minimum, maximum, and mean) were all ≤0.1 Gy. For the composite-shot plans, however, the dose differences increased as the phantom was shifted through positions B-D, with a gamma index passing rate of 61% for lesion-E in position D, and 92%, 79%, and 45% for lesion-S in positions B, C, and D, respectively.ConclusionsPlans using only uniform shots are more robust to deviations in treatment position. The tolerance for such deviations may be lower for plans using composite shots.