The LundADose method for planar image activity quantification and absorbed-dose assessment in radionuclide therapy

A new method for absorbed-dose assessment in radionuclide therapy is presented in this paper. The method is based on activity quantification by the conjugate-view methodology, applied to serial whole-body, anterior-posterior, scintillation-camera scans. The quantification method is an extension of previous studies, and includes separate corrections for attenuation, scatter, and overlapping organs. Further development has now been undertaken to take into account the capabilities of new dual-head camera systems with a built-in X-ray tube for anatomical imaging. Furthermore, the modeling of time-activity data is included, and dosimetric calculations based on the formalism by the Medical Internal Radiation Dose (MIRD) committee. To streamline absorbed-dose assessments for a large number of patient studies, the programs for quantification, image registration, and absorbed-dose calculations have been embedded in an envelop program termed LundADose, where calculations, to a great extent, are performed automatically. Evaluation of the whole-body activity quantification is performed for patients undergoing radioimmunotherapy by monoclonal antibodies labeled with (111)In or (90)Y.     

3D absorbed dose calculations based on SPECT: evaluation for 111-In/90-Y therapy using Monte Carlo simulations

A general method is presented for patient-specific three-dimensional (3D) absorbed dose calculations based on quantitative SPECT activity measurements. The computational scheme includes a method for registration of the CT study to the SPECT image, and compensation for attenuation, scatter, and collimator-detector response including septal penetration, performed as part of an iterative reconstruction method. From SPECT images, the absorbed dose rate is calculated using an EGS4 Monte Carlo code, which converts the activity distribution to an absorbed dose rate distribution. Evaluation of the accuracy in the activity quantification and the absorbed dose calculation is based on realistic Monte Carlo simulated SPECT data of a voxel-computer phantom and (111)In and (90)Y. Septal penetration was not included in this study. The SPECT-based activity concentrations and absorbed dose distributions are compared to the actual values; the results imply that the corrections for attenuation and scatter yield results of high accuracy. The presented method includes compensation for most parameters deteriorating the quantitative image information. Inaccuracies are, however, introduced by the limited spatial resolution of the SPECT system, which are not fully compensated by the collimator-response correction. The proposed evaluation methodology may be used as a basis for future inter-comparison of different dosimetry calculation schemes.     

Voxeldoes: a computer program for 3-D dose calculation in therapeutic nuclear medicine

A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: (i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; (ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and (iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.     

Comparison of image quality of different iodine isotopes (I-123, I-124, and I-131)

I-131 is a frequently used isotope for radionuclide therapy. This technique for cancer treatment requires a pre-therapeutic dosimetric study. The latter is usually performed (for this radionuclide) by directly imaging the uptake of the therapeutic radionuclide in the body or by replacing it by one of its isotopes, which are more suitable for imaging. This study aimed to compare the image quality that can be achieved by three iodine isotopes: I-131 and I-123 for single-photon emission computed tomography imaging, and I-124 for positron emission tomography imaging. The imaging characteristics of each isotope were investigated by simulated data. Their spectrums, point-spread functions, and contrast-recovery curves were drawn and compared. I-131 was imaged with a high-energy all-purpose (HEAP) collimator, whereas two collimators were compared for I-123: low-energy high-resolution (LEHR) and medium energy (ME). No mechanical collimation was used for I-124. The influence of small high-energy peaks (>0.1%) on the main energy window contamination were evaluated. Furthermore, the effect of a scattering medium was investigated and the triple energy window (TEW) correction was used for spectral-based scatter correction. Results showed that I-123 gave the best results with a LEHR collimator when the scatter correction was applied. Without correction, the ME collimator reduced the effects of high-energy contamination. I-131 offered the worst results. This can be explained by the large amount of septal penetration from the photopeak and by the collimator, which gave a low spatial resolution. I-124 gave the best imaging properties owing to its electronic collimation (high sensitivity) and a short coincidence time window.     

RMDP: a dedicated package for 131I SPECT quantification,registration and patient-specific dosimetry

The limitations of traditional targeted radionuclide therapy (TRT) dosimetry can be overcome by using voxel-based techniques. All dosimetry techniques are reliant on a sequence of quantitative emission and transmission data. The use of (131)I, for example, with NaI or mIBG, presents additional quantification challenges beyond those encountered in low-energy NM diagnostic imaging, including dead-time correction and additional photon scatter and penetration in the camera head. The Royal Marsden Dosimetry Package (RMDP) offers a complete package for the accurate processing and analysis of raw emission and transmission patient data. Quantitative SPECT reconstruction is possible using either FBP or OS-EM algorithms. Manual, marker- or voxel-based registration can be used to register images from different modalities and the sequence of SPECT studies required for 3-D dosimetry calculations. The 3-D patient-specific dosimetry routines, using either a beta-kernel or voxel S-factor, are included. Phase-fitting each voxel's activity series enables more robust maps to be generated in the presence of imaging noise, such as is encountered during late, low-count scans or when there is significant redistribution within the VOI between scans. Error analysis can be applied to each generated dose-map. Patients receiving (131)I-mIBG, (131)I-NaI, and (186)Re-HEDP therapies have been analyzed using RMDP. A Monte-Carlo package, developed specifically to address the problems of (131)I quantification by including full photon interactions in a hexagonal-hole collimator and the gamma camera crystal, has been included in the dosimetry package. It is hoped that the addition of this code will lead to improved (131)I image quantification and will contribute towards more accurate 3-D dosimetry.     

Monte Carlo modeling of gamma cameras for I-131 imaging in targeted radiotherapy

INTRODUCTION: Dosimetric studies for targeted radiotherapy require the quantification of activity from scintigraphic images. Quantitative imaging is difficult to achieve because of several effects that can lead to errors in activity estimates, some of which are more apparent when I-131 is considered as a source. An evaluation of these phenomena was performed by modeling the gamma camera and its behavior using Monte Carlo simulations. Two gamma cameras were modeled: DST-XLi and Millennium VG Hawk-Eye (GEMS), and two Monte Carlo codes were used: MCNP (LANL) and GATE (openGate collaboration). GATE is a dedicated single photon emission computed tomography/positron emission tomography (SPECT)/(PET) software based on Geant4 (CERN, Geneve). MATERIALS AND METHODS: Gamma-camera modeling was performed in 2 steps: first without a collimator, then with a high-energy, all-purpose (HEAP) collimator according to the specifications given by the manufacturer (the simulation took the hexagonal shape of collimator holes into account). Simulated and measured energy spectra from point sources in air were compared (with or without a collimator). Spatial resolution was obtained from line sources in air at various distances from the detector heads. The photons detected in the 20% energy window from a point source were analyzed in order to determine the amount of primary photons, scattered photons (in the collimator), and septal photons (i.e., photons that crossed the collimator septa without interacting). RESULTS: Both codes agree well with experimental measurements for the two gamma cameras considered in this study. This allowed us to validate gamma-camera modeling and also served as a benchmark of GATE (new code) versus MCNP (reference code). As shown previously by Dewaraja et al., septal penetration is an important source of image degradation when HEAP collimators are used for I-131 imaging. With the DST-XLi, and for a point source in air, our simulations have shown that 53% of scattered (30%) and septal penetration (23%) photons are detected in the 20% window. CONCLUSION: The modeling of two gamma cameras (DST-XLi and Millennium VG Hawk-Eye) has been performed with two Monte Carlo codes (MCNP and Gate). Results obtained with the two Monte Carlo codes agree well with experimental results. As already indicated by several authors, septal penetration and scattered photons in the collimator have a major impact on I-131 scintigraphic imaging.     

The value of narrow CT window settings in the recognition of subtle acute aortic intramural haematoma

Four patients with acute aortic intramural haematoma are presented. In all patients the typical crescentic hyperdense rim within the aortic wall was not obvious on unenhanced CT when reviewed on standard mediastinal windows, but the hyperdense crescentic rim was well seen on narrow window settings. The findings suggest that all patients with a typical clinical presentation of acute thoracic aortic dissection who do not have a classical dissection on contrast-enhanced CT or a hyperdense intramural haematoma on standard mediastinal settings, should have the non-contrast scans reviewed on narrow window settings.     

Dual-modality imaging of cancer with SPECT/CT

Dual-modality imaging is an in vivo diagnostic technique that obtains structural and functional information directly from patient studies in a way that cannot be achieved with separate imaging systems alone. Dual-modality imaging systems are configured by combining computed tomography (CT) with radionuclide imaging (using positron emission tomography (PET) or single-photon emission computed tomography (SPECT)) on a single gantry which allows both functional and structural imaging to be performed during a single imaging session without having the patient leave the imaging system. A SPECT/CT system developed at UCSF is being used in a study to determine if dual-modality imaging offers advantages for assessment of patients with prostate cancer using (111)In-ProstaScint, a radiolabeled antibody for the prostate-specific membrane antigen. (111)In-ProstaScint images are reconstructed using an iterative maximum-likelihood expectation-maximization (ML-EM) algorithm with correction for photon attenuation using a patient-specific map of attenuation coefficients derived from CT. The ML-EM algorithm accounts for the dual-photon nature of the 111In-labeled radionuclide, and incorporates correction for the geometric response of the radionuclide collimator. The radionuclide image then can be coregistered and overlaid in color on a grayscale CT image for improved localization of the functional information from SPECT. Radionuclide images obtained with SPECT/CT and reconstructed using ML-EM with correction for photon attenuation and collimator response improve image quality in comparison to conventional radionuclide images obtained with filtered backprojection reconstruction. These results illustrate the potential advantages of dual-modality imaging for improving the quality and the localization of radionuclide uptake for staging disease, planning treatment, and monitoring therapeutic response in patients with cancer.     

Observer variation in target volume delineation of lung cancer related to radiation oncologist-computer interaction: a 'Big Brother' evaluation.

BACKGROUND AND PURPOSE: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. PATIENTS AND METHODS: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume (GTV) including positive lymph nodes of 22 lung cancer patients (stages I-IIIB) on CT only. All radiation oncologist-computer interactions were recorded with a tool called 'Big Brother'. For each radiation oncologist and patient the following issues were analyzed: delineation time, number of delineated points and corrections, zoom levels, level and window (L/W) settings, CT slice changes, use of side windows (coronal and sagittal) and software button use. RESULTS: The mean delineation time per GTV was 16 min (SD 10 min). The mean delineation time for lymph node positive patients was on average 3 min larger (P = 0.02) than for lymph node negative patients. Many corrections (55%) were due to L/W change (e.g. delineating in mediastinum L/W and then correcting in lung L/W). For the lymph node region, a relatively large number of corrections was found (3.7 corr/cm2), indicating that it was difficult to delineate lymph nodes. For the tumor-atelectasis region, a relative small number of corrections was found (1.0 corr/cm2), indicating that including or excluding atelectasis into the GTV was a clinical decision. Inappropriate use of L/W settings was frequently found (e.g. 46% of all delineated points in the tumor-lung region were delineated in mediastinum L/W settings). Despite a large observer variation in cranial and caudal direction of 0.72 cm (1 SD), the coronal and sagittal side windows were not used in 45 and 60% of the cases, respectively. For the more difficult cases, observer variation was smaller when the coronal and sagittal side windows were used. CONCLUSIONS: With the 'Big Brother' tool a method was developed to trace the delineation process. The differences between observers concerning the delineation style were large. This study led to recommendations on how to improve delineation accuracy by adapting the delineation protocol (guidelines for L/W use) and delineation software (double window with lung and mediastinum L/W settings at the same time, enforced use of coronal and sagittal views) and including FDG-PET information (lymph nodes and atelectasis).     

The impact of PET and SPECT on dosimetry for targeted radionuclide therapy

Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for a range of cancers. To date, few treatments have involved the use of dosimetry either to plan treatment or to retrospectively ascertain the absorbed dose delivered during treatment. Also the correlation between absorbed dose and biological effect has been difficult to establish. Tomographic methods permit the determination of the activity volume on a macroscopic scale at different time points. Proper attenuation correction in tomographic imaging requires a patient-specific attenuation map. This can be obtained from scintillation-camera transmission scanning, CT or by using segmented scatter-emission images. Attenuation corrections can be performed either on the projection images, on the reconstructed images, or as part of an iterative reconstruction method. The problem of image quantification for therapy radionuclides, particularly for I-131, is exacerbated by the fact that most cameras are optimised for diagnostic imaging with Tc-99m. In addition, problems may arise when high activities are to be measured due to count losses and mis-positioned events, because of insufficient pile-up and dead time correction methods. Sufficient image quantification, however is only possible if all effects that degrade the quantitative content of the image have been corrected for. Monte Carlo simulations are an appealing tool that can help to model interactions occurring in the patient or in the detector system. This is helpful to develop and test correction techniques, or to help to define detectors better suited to quantitative imaging. PET is probably the most accurate imaging method for the determination of activity concentrations in tissue. PET imaging can be considered for pre-therapeutic treatment planning but ideally requires the use of a radioisotope from the same element as that used for treatment (e.g. I-124 for I-131; Y-86 for Y-90). Problems, however are that--some of the positron emitting isotopes have a shorter half-life--non-standard quantification procedures have to be performed--the availability of the radiopharmaceutical is presently limited; Many 3D-tools and -techniques are now available to the physicist and clinician to enable absorbed dose calculations to both target and critical organs-at-risk. The challenge now facing nuclear medicine is to enable this methodology to be routinely available to the clinic, to ensure common standard operating procedures between centres and in particular to correlate response criteria with absorbed dose estimates.     

Near-infrared characterization of breast tumors in vivo using spectrally-constrained reconstruction

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34-86% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors.     

Cone-beam-CT guided radiation therapy: technical implementation.

BACKGROUND AND PURPOSE: X-ray volumetric imaging system (XVI) mounted on a linear accelerator is available for image guidance applications. In preparation for clinical implementation, phantom and patient imaging studies were conducted to determine the irradiation parameters that would trade-off image quality, patient dose and scanning time. PATIENTS AND METHODS: The XVI image quality and imaging dose were benchmarked against those obtained with a helical CT scanner for a head and body phantom. The irradiation parameters were varied including the total imaging dose, number of projections, field of view, reconstruction resolution and use of a scatter rejection grid. We characterized the image quality based on relative contrast, noise, contrast to noise ratio (CNR) and point spread function (PSF). XVI scans of pelvis, head and neck and lung patients were acquired and submitted to a range of observers to identify the favorable reconstruction parameters. RESULTS: Phantom studies have demonstrated that a scatter rejection grid reduces photon scattering and improves the image uniformity. For the body phantom, the helical CT and the wide field XVI technique produce similar image quality, with surface doses of 0.025 and 0.044 Gy respectively. We have demonstrated that the local tomography technique improves the image contrast and the CNR while reducing the skin dose by 40-50% compared to the wide field technique. Clinical scans of head and neck, lung and prostate patients present good soft tissue contrast and excellent bone definition. CONCLUSIONS: With adjustment of irradiation parameters and an imaging surface dose of less than 0.05 Gy, high quality XVI images can be obtained for a phantom simulating the body thickness. XVI is currently feasible for image-guided treatments of head and neck, torso and pelvic areas using soft tissue and bony structures.     

Comparison between 2D and 3D dosimetry protocols in 90Y-ibritumomab tiuxetan radioimmunotherapy of patients with non-Hodgkin's lymphoma

We compared the radiation-absorbed dose obtained from a two dimensional (2D) protocol, based on planar whole-body (WB) scans and fixed reference organ masses with dose estimates, using a 3D single-photon emission computed tomography (SPECT) imaging protocol and patient-specific organ masses. METHODS: Six (6) patients with follicular non-Hodgkin's lymphoma underwent a computed tomography (CT) scan, 5 2D planar WB, and 5 SPECT scans between days 0 and 6 after the injection of (111)In-ibritumomab tiuxetan. The activity values in the liver, spleen, and kidneys were calculated from the 2D WB scans, and also from the 3D SPECT images reconstructed, using quantitative image processing. Absorbed doses after the administration of (90)Y-ibritumomab tiuxetan were calculated from the (111)In WB activity values combined with reference organ masses and also from the SPECT activity values and organ masses as estimated from the patient CT scan. To assess the quantitative accuracy of the WB and SPECT scans, an abdominal phantom was also studied. RESULTS: The differences between organ masses estimated from the patient CT and from the reference MIRD models were between -10% and +98%. Using the phantom, errors in organ and tumor activity estimates were between -86% and 10% for the WB protocol and between -43% and -6% for the SPECT protocol. Patient liver, spleen, and kidney activity values determined from SPECT were systematically less than those from the WB scans. Radiation-absorbed doses calculated with the 3D protocol were systematically lower than those calculated from the WB protocol (29%+/-26%, 73%+/-26%, and 33%+/-53% differences in the liver, spleen, and kidney, respectively), except in the kidneys of 2 patients and in the liver of 1 patient. CONCLUSIONS:Accounting for patient-specific organ mass and using SPECT activity quantification have both a great impact on estimated absorbed doses.     

Comparison of long-axis and short-axis PROPELLER-EPI for diffusion-weighted Magnetic Resonance Imaging

Echo planar imaging (EPI) in combination with PROPELLER allows high-resolution diffusion-weighted imaging. In this study, the image quality of short-axis and long-axis PROPELLER was compared and optimized using phantom and in vivo data. Furthermore, diffusion-weighted measurements using both sequences were compared with those of a reference sequence. It was found that the long-axis sequence provided better image quality, whereas the results of the diffusion weighted measurements were more accurate with the short-axis variant. and that the results of the diffusion weighted measurements of both sequences agreed well with those of the reference sequence.     

Secondary neutron dose during proton therapy using spot scanning

PURPOSE: During proton radiotherapy, secondary neutrons are produced by nuclear interactions in the material in the beam line before and after entering the patient. The dose equivalent deposited by these neutrons is usually not considered in routine treatment planning. In this study, we estimated the neutron dose in patients from a spot scanning beam line by performing measurements and Monte Carlo simulations. METHODS AND MATERIALS: Measurements of the secondary neutron dose were performed during irradiation of a water phantom with 177-MeV protons using a Bonner sphere and CR39 etch detectors. Additionally, Monte Carlo simulations were performed using the FLUKA code. RESULTS: A comparison of our measurements with measurements taken at a beam line using the scatter foil technique shows a dose advantage of at least 10 for the spot scanning technique. In the region of the Bragg peak, the neutron dose equivalent can reach for a medium-sized target volume approximately 1% of the treatment dose. Neutron doses expected in healthy tissues of the patient (in the not-treated volume) are for large and medium target volumes, approximately 0.004 Sv and 0.002 Sv per treatment Gy, respectively. CONCLUSIONS: We conclude from the measurements and simulations that the dose deposited by secondary neutrons during proton radiotherapy using the spot scanning technique can be neglected in the treatment region. In the healthy tissue, the dose coming from neutrons (0.002 Sv per treatment Gy) is approximately a factor of two larger than during photon treatment (0.001 Sv). These contributions to the integral dose from neutrons are still very low when compared to the dose sparing that can be achieved by using a proton beam instead of photons.     

Imaging tumor folate receptors using 111In-DTPA-methotrexate

It is known that membrane folic acid receptors are responsible for cellular accumulation of folate and folate analogs, such as methotrexate, and overexpressed on various tumor cells. This study was aimed to develop an 111In labelled DTPA-methotrexate (DTPA-MTX) to image tumor folate receptors in vivo. DTPA-MTX was synthesized by reacting ethylenediamine with MTX. The resulting amino analogue of MTX was reacted with DTPA dianhydride in basic aqueous solution followed by dialysis. Tissue distribution was determined in breast tumor-bearing rats at 0.5, 2, 24, and 48 h (n = 3/time interval). To determine receptor-mediated process 111In-DTPA-MTX was co-administrated with varying blocking doses of cold folate to tumor-bearing rats. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using 111In-DTPA. In animal studies, tumor/blood count density ratios at 0.5-48 h gradually increased from 0.8 +/- 0.32 to 2.2 +/- 0.41 with 111In-DTPA-MTX. Conversely, these values showed time-dependent decrease from 1.19 +/- 0.69 to 0.56 +/- 0.10 with 111In-DTPA in the same time period. Tumor/muscle and tumor/blood count density ratios significantly decreased with high doses of folic acid co-administration. Planar images and autoradiograms confirmed that the tumors could be visualized acceptably with 111In-DTPA-MTX. The results indicate the feasibility of using 111In-DTPA-MTX to image tumors through a folate receptor-mediated process.     

Primary photon fluence extraction from portal images acquired with an amorphous silicon flat panel detector: experimental determination of a scatter filter

When dose delivery to the patient is evaluated by extracting the primary photon fluence impinging on a portal imaging device, scattered radiation from the patient acts as noise. Our aim in the present study is to establish and test a procedure to filter out scatter radiations from portal images by experimental determination of a scatter filtering function. We performed a dose calibration of the Varian (Varian Medical Systems, Palo Alto, CA) aS500 electronic portal imaging device in routine use in our institution. We then analyzed the collected data and extracted the scatter filtering function by applying a simple scatter model with the aid of home-made software. To check the reliability of our calculations we compared central axis dose values in a PMMA phantom computed using the extracted primary fluence with those obtained from experimental TMR(0) tabulated values obtaining a agreement within about 3%. We finally performed a check of dose delivery repeatability by calculating the dose delivered to the EPID during portal image acquisition for patient positioning. Delivered dose per MU fluctuations were within 5% over a set of images acquired during routine use with no prior application of any procedure aimed at optimizing dosimetric repeatability.     

Immunohistochemical image analysis of estrogen and progesterone receptors in breast cancer

Background  Recently objective quantification of immunohistochemical estrogen receptor (ER) and progesterone receptor (PgR) staining in breast cancer by image cytometry has been predominantly performed by measuring the area of positively stained cells. However, in sample preparations of immunostained hormone receptors, both the stained area and the intensity of staining vary. In this study, we performed quantification of the stained area by measuring, tailing intensity using image cytometry. Methods  Quantitative analysis of ER and PgR immunohistochemistry was performed using image cytometry. The obtained values were presented as % of positive staining (%PS). Comparison of %PS with values obtained by EIA and with clinicopathological features was performed. Results  The %PS values and the natural logarithm of the EIA levels of the hormone receptors showed a significant positive correlation for both ER and PgR. The concordance of the results obtained by the two methods was 96.3% for ER and 73.7% for PgR. The ER-%PS values of postmenopausal patients were significantly higher than those of premenopausal patients, whereas the PgR-%PS values of the former group were significantly lower than those of the latter group. Conclusions  The quantification of ER and PgR in immunostained preparations using %PS as a parameter was reproducible and showed a high correlation with values obtained by EIA. It was shown that only menopausal status affects hormone receptor levels when analyzing the relationship between %PS measurements and clinicopathological features.     

Impact of scatter and attenuation corrections for iodine-131 two-dimensional quantitative imaging in patients

This study assessed the impact of scatter and attenuation corrections on the estimated activity delivered to whole body and liver in five patients included in a radioimmunotherapy clinical trial. Before injection of the radiopharmaceutical, transmission images were acquired with the Transmission Attenuation Correction - Whole-body (SMVi-GEMS) prototype. Emission images were obtained in energy-indexed list mode at least four times after injection. 20% window and scatter-corrected images (Dual Energy Window-DEW and Triple Energy Window-TEW) were generated. Whole-body activity was calculated 1-h after injection (and compared with injected activity). Cumulated activities in whole body and liver were determined according to the geometric mean approach. The mean relative error made in estimations of whole-body activity at 1-h was 6.9+/-10.3% without corrections. Taking scatter into account led to underestimation, but reduced the influence of patient morphotype (-40.0+/-7.6% and -43.3+/-6.2% for DEW and TEW). Attenuation correction led to a large overestimation, whether used alone (155.2+/-39.0%) or associated with scatter correction (39.6+/-10.4% and 35.9+/-10.2% for DEW and TEW). Compared to the geometric mean alone, scatter correction led to a reduction of cumulated activities of around 45% for whole body and less than 30% for liver. Attenuation correction had a more marked impact, particularly for liver where estimated cumulated activity increased from 150 to 300%. Preliminary scatter correction limited the increase to 100% for DEW and 150% for TEW in liver and to 25% for both DEW and TEW in whole body. Although this would probably be different at the organ level, the calculation of whole-body activity without scatter and attenuation correction gave the lowest biases. But from a scientific point of view, this cannot be a satisfactory method. Attenuation correction has a greater impact than scatter correction. The association of both corrections is not sufficient to obtain accurate absolute quantification. Other factors limit planar quantification with iodine-131, notably auto-absorption of sources, septal penetration of high-energy photons through the collimator and superimposition of sources.     

Development and Monte Carlo analysis of antiscatter grids for mammography

Mammography arguably demands the highest fidelity of all x-ray imaging applications, with simultaneous requirements of exceedingly high spatial and contrast resolution. Continuing technical improvements of screen-film and digital mammography systems have led to substantial improvements in image quality, and therefore improvements in the performance of anti-scatter grids are required to keep pace with the improvements in other components of the imaging chain. The development of an air-core honeycomb (cellular) grid using x-ray lithography and electroforming techniques is described, and the production of a 60 mm x 60 mm section of grid is reported. A crossed grid was constructed with 25 microm copper septa, and a period of 550 microm. Monte Carlo and numerical simulation methods were used to analyze the theoretical performance of the fabricated grid, and comparisons with other grid systems (Lorad HTC and carbon fiber interspaced grids) were made over a range of grid ratios. The results demonstrate essentially equivalent performance in terms of contrast improvement factor (CIF) and Bucky factor (BF) between Cu and Au honeycomb grids and the Lorad HTC (itself a copper honeycomb grid). Gold septa improved both CIF and BF performance in higher kVp, higher scatter geometries. The selectivity of honeycomb grids was far better than for linear grids, with a factor of approximately 3.9 improvement at a grid ratio of 5.0. It is concluded that using the fabrication methods described, that practical honeycomb grid structures could be produced for use in mammographic imaging, and that a substantial improvement in scatter rejection would be achieved using these devices.