Targeted multi-pinhole SPECT.

PURPOSE: Small-animal single photon emission computed tomography (SPECT) with focused multi-pinhole collimation geometries allows scanning modes in which large amounts of photons can be collected from specific volumes of interest. Here we present new tools that improve targeted imaging of specific organs and tumours, and validate the effects of improved targeting of the pinhole focus. METHODS: A SPECT system with 75 pinholes and stationary detectors was used (U-SPECT-II). An XYZ stage automatically translates the animal bed with a specific sequence in order to scan a selected volume of interest. Prior to stepping the animal through the collimator, integrated webcams acquire images of the animal. Using sliders, the user designates the desired volume to be scanned (e.g. a xenograft or specific organ) on these optical images. Optionally projections of an atlas are overlaid semiautomatically to locate specific organs. In order to assess the effects of more targeted imaging, scans of a resolution phantom and a mouse myocardial phantom, as well as in vivo mouse cardiac and tumour scans, were acquired with increased levels of targeting. Differences were evaluated in terms of count yield, hot rod visibility and contrast-to-noise ratio. RESULTS: By restricting focused SPECT scans to a 1.13-ml resolution phantom, count yield was increased by a factor 3.6, and visibility of small structures was significantly enhanced. At equal noise levels, the small-lesion contrast measured in the myocardial phantom was increased by 42%. Noise in in vivo images of a tumour and the mouse heart was significantly reduced. CONCLUSION: Targeted pinhole SPECT improves images and can be used to shorten scan times. Scan planning with optical cameras provides an effective tool to exploit this principle without the necessity for additional X-ray CT imaging.

Minimizing the need for coil attenuation correction in integrated PET/MRI at 1.5 T using low-density MR-linac receive arrays.

The simultaneous use of positron emission tomography (PET) and magnetic resonance imaging (MRI) requires attenuation correction (AC) of photon-attenuating objects, such as MRI receive arrays. However, AC of flexible, on-body arrays is complex and therefore often omitted. This can lead to significant, spatially varying PET signal losses when conventional MRI receive arrays are used. Only few dedicated, photon transparent PET/MRI arrays exist, none of which are compatible with our new, wide-bore 1.5 T PET/MRI system dedicated to radiotherapy planning. In this work, we investigated the use of 1.5 T MR-linac (MRL) receive arrays for PET/MRI, as these were designed to have a low photon attenuation for accurate dose delivery and can be connected to the new 1.5 T PET/MRI scanner. Three arrays were assessed: an 8-channel clinically-used MRL array, a 32-channel prototype MRL array, and a conventional MRI receive array. We experimentally determined, simulated, and compared the impact of these arrays on the PET sensitivity and image reconstructions. Furthermore, MRI performance was compared. Overall coil-induced PET sensitivity losses were reduced from 8.5% (conventional) to 1.7% (clinical MRL) and 0.7% (prototype MRL). Phantom measurements showed local signal errors of up to 32.7% (conventional) versus 3.6% (clinical MRL) and 3.5% (prototype MRL). Simulations with data of eight cancer patients showed average signal losses were reduced from 14.3% (conventional) to 1.2% (clinical MRL) and 1.0% (prototype MRL). MRI data showed that the signal-to-noise ratio of the MRL arrays was slightly lower at depth (110 versus 135). The parallel imaging performance of the conventional and prototype MRL arrays was similar, while the clinical MRL array's performance was lower. In conclusion, MRL arrays reducein-vivoPET signal losses >10×, which decreases, or eliminates, the need for coil AC on a new 1.5 T PET/MRI system. The prototype MRL array allows flexible coil positioning without compromising PET or MRI performance. One limitation of MRL arrays is their limited radiolucent PET window (field of view) in the craniocaudal direction.

Evaluation of the radiofrequency performance of a wide-bore 1.5 T positron emission tomography/magnetic resonance imaging body coil for radiotherapy planning.

BACKGROUND AND PURPOSE: The restricted bore diameter of current simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) systems can be an impediment to achieving similar patient positioning during PET/MRI planning and radiotherapy. Our goal was to evaluate the B1 transmit (B1 +) uniformity, B1 + efficiency, and specific absorption rate (SAR) of a novel radiofrequency (RF) body coil design, in which RF shielded PET detectors were integrated with the specific aim of enabling a wide-bore PET/MRI system. MATERIALS AND METHODS: We designed and constructed a wide-bore PET/MRI RF body coil to be integrated with a clinical MRI system. To increase its inner bore diameter, the PET detectors were positioned between the conductors and the RF shield of the RF body coil. Simulations and experiments with phantoms and human volunteers were performed to compare the B1 + uniformity, B1 + efficiency, and SAR between our design and the clinical body coil. RESULTS: In the simulations, our design achieved nearly the same B1 + field uniformity as the clinical body coil and an almost identical SAR distribution. The uniformity findings were confirmed by the physical experiments. The B1 + efficiency was 38% lower compared to the clinical body coil. CONCLUSIONS: To achieve wide-bore PET/MRI, it is possible to integrate shielding for PET detectors between the body coil conductors and the RF shield without compromising MRI performance. Reduced B1 + efficiency may be compensated by adding a second RF amplifier. This finding may facilitate the application of simultaneous whole-body PET/MRI in radiotherapy planning.

U-SPECT-II: An Ultra-High-Resolution Device for Molecular Small-Animal Imaging.

UNLABELLED: We present a new rodent SPECT system (U-SPECT-II) that enables molecular imaging of murine organs down to resolutions of less than half a millimeter and high-resolution total-body imaging. METHODS: The U-SPECT-II is based on a triangular stationary detector set-up, an XYZ stage that moves the animal during scanning, and interchangeable cylindric collimators (each containing 75 pinhole apertures) for both mouse and rat imaging. A novel graphical user interface incorporating preselection of the field of view with the aid of optical images of the animal focuses the pinholes to the area of interest, thereby maximizing sensitivity for the task at hand. Images are obtained from list-mode data using statistical reconstruction that takes system blurring into account to increase resolution. RESULTS: For (99m)Tc, resolutions determined with capillary phantoms were smaller than 0.35 and 0.45 mm using the mouse collimator with 0.35- and 0.6-mm pinholes, respectively, and less than 0.8 mm using the rat collimator with 1.0-mm pinholes. Peak geometric sensitivity is 0.07% and 0.18% for the mouse collimator with 0.35- and 0.6-mm pinholes, respectively, and 0.09% for the rat collimator. Resolution with (111)In, compared with that with (99m)Tc, was barely degraded, and resolution with (125)I was degraded by about 10%, with some additional distortion. In vivo, kidney, tumor, and bone images illustrated that U-SPECT-II could be used for novel applications in the study of dynamic biologic systems and radiopharmaceuticals at the suborgan level. CONCLUSION: Images and movies obtained with U-SPECT-II provide high-resolution radiomolecule visualization in rodents. Discrimination of molecule concentrations between adjacent volumes of about 0.04 microL in mice and 0.5 microL in rats with U-SPECT-II is readily possible.

Accelerated SPECT image reconstruction with FBP and an image enhancement convolutional neural network.

BACKGROUND: Monte Carlo-based iterative reconstruction to correct for photon scatter and collimator effects has been proven to be superior over analytical correction schemes in single-photon emission computed tomography (SPECT/CT), but it is currently not commonly used in daily clinical practice due to the long associated reconstruction times. We propose to use a convolutional neural network (CNN) to upgrade fast filtered back projection (FBP) image quality so that reconstructions comparable in quality to the Monte Carlo-based reconstruction can be obtained within seconds. RESULTS: A total of 128 technetium-99m macroaggregated albumin pre-treatment SPECT/CT scans used to guide hepatic radioembolization were available. Four reconstruction methods were compared: FBP, clinical reconstruction, Monte Carlo-based reconstruction, and the neural network approach. The CNN generated reconstructions in 5 sec, whereas clinical reconstruction took 5 min and the Monte Carlo-based reconstruction took 19 min. The mean squared error of the neural network approach in the validation set was between that of the Monte Carlo-based and clinical reconstruction, and the lung shunting fraction difference was lower than 2 percent point. A phantom experiment showed that quantitative measures required in radioembolization were accurately retrieved from the CNN-generated reconstructions. CONCLUSIONS: FBP with an image enhancement neural network provides SPECT reconstructions with quality close to that obtained with Monte Carlo-based reconstruction within seconds.

Technical Note: Validation of two methods to determine contact area between breast and compression paddle in mammography.

PURPOSE: To assess the accuracy of two methods of determining the contact area between the compression paddle and the breast in mammography. An accurate method to determine the contact area is essential to accurately calculate the average compression pressure applied by the paddle. METHODS: For a set of 300 breast compressions, we measured the contact areas between breast and paddle, both capacitively using a transparent foil with indium-tin-oxide (ITO) coating attached to the paddle, and retrospectively from the obtained mammograms using image processing software (Volpara Enterprise, algorithm version 1.5.2). A gold standard was obtained from video images of the compressed breast. During each compression, the breast was illuminated from the sides in order to create a dark shadow on the video image where the breast was in contact with the compression paddle. We manually segmented the shadows captured at the time of x-ray exposure and measured their areas. RESULTS: We found a strong correlation between the manual segmentations and the capacitive measurements [r = 0.989, 95% CI (0.987, 0.992)] and between the manual segmentations and the image processing software [r = 0.978, 95% CI (0.972, 0.982)]. Bland-Altman analysis showed a bias of -0.0038 dm2 for the capacitive measurement (SD 0.0658, 95% limits of agreement [-0.1329, 0.1252]) and -0.0035 dm2 for the image processing software [SD 0.0962, 95% limits of agreement (-0.1921, 0.1850)]. CONCLUSIONS: The size of the contact area between the paddle and the breast can be determined accurately and precisely, both in real-time using the capacitive method, and retrospectively using image processing software. This result is beneficial for scientific research, data analysis and quality control systems that depend on one of these two methods for determining the average pressure on the breast during mammographic compression.

Towards personalized compression in mammography: a comparison study between pressure- and force-standardization.

OBJECTIVE: To compare a conventional 14 decanewton (daN) force-standardized compression protocol with a personalized 10kilopascal (kPa) pressure-standardized protocol. METHODS: A new add-on contact area detector, which enables pressure-standardized compression, is validated in a double-blinded intra-individual comparison study. Breast screening participants (433) received one craniocaudal (CC) and one mediolateral oblique (MLO) compression for both breasts. Three of these compressions were force-standardized, and one, blinded and randomly assigned, was pressure-standardized. Participants scored their pain experience on an 11-point numerical rating scale (NRS). Three experienced breast-screening radiologists, blinded for compression protocol, indicated which images required retakes. RESULTS: An unanticipated under-compression issue that occurred at forces below 5daN was effectively solved with minimal extra radiographer training during the study. For pressure-standardized compressions obtained at 5daN or more, the compressed breasts thickness increased on average 4.2% (MLO)-6.3% (CC), average pain scores were reduced by 10% (MLO)-17% (CC) and the proportion of women experiencing severe pain (NRS≥7) was reduced by 27% (MLO)-32% (CC), compared with force-standardized compressions (all p-values <0.05). Average glandular dose (AGD) and proportions of retakes were similar for both protocols. CONCLUSION: Pressure-standardized compressions resulted in AGD values and a retake proportion similar to force-standardized compressions, while pain was significantly reduced.

Mammographic compression--a need for mechanical standardization.

BACKGROUND: A lack of consistent guidelines regarding mammographic compression has led to wide variation in its technical execution. Breast compression is accomplished by means of a compression paddle, resulting in a certain contact area between the paddle and the breast. This procedure is associated with varying levels of discomfort or pain. On current mammography systems, the only mechanical parameter available in estimating the degree of compression is the physical entity of force (daN). Recently, researchers have suggested that pressure (kPa), resulting from a specific force divided by contact area on a breast, might be a more appropriate parameter for standardization. Software has now become available which enables device-independent cross-comparisons of key mammographic metrics, such as applied compression pressure (force divided by contact area), breast density and radiation dose, between patient populations. PURPOSE: To compare the current compression practice in mammography between different imaging sites in the Netherlands and the United States from a mechanical point of view, and to investigate whether the compression protocols in these countries can be improved by standardization of pressure (kPa) as an objective mechanical parameter. MATERIALS AND METHODS: We retrospectively studied the available parameters of a set of 37,518 mammographic compressions (9188 women) from the Dutch national breast cancer screening programme (NL data set) and of another set of 7171 compressions (1851 women) from a breast imaging centre in Pittsburgh, PA (US data set). Both sets were processed using VolparaAnalytics and VolparaDensity to obtain the applied average force, pressure, breast thickness, breast volume, breast density and average glandular dose (AGD) as a function of the size of the contact area between the breast and the paddle. RESULTS: On average, the forces and pressures applied in the NL data set were significantly higher than in the US data set. The relative standard deviation was larger in the US data set than in the NL data set. Breasts were compressed with a force in the high range of >15 daN for 31.1% and >20 kPa for 12.3% of the NL data set versus, respectively, 1.5% and 1.7% of the US data set. In the low range we encountered compressions with a pressure of <5 daN for 21.1% and <5 kPa for 21.7% of the US data set versus, respectively, 0.05% and 0.6% in the NL data set. Both the average and the standard deviation of the AGD were higher in the US data set. CONCLUSION: (1) Current mammographic breast compression policies lead to a wide range of applied forces and pressures, with large variations both within and between clinical sites. (2) Pressure standardization could decrease variation, improve reproducibility, and reduce the risk of unnecessary pain, unnecessary high radiation doses and inadequate image quality.

Three-dimensional histologic validation of high-resolution SPECT of antibody distributions within xenografts.

UNLABELLED: Longitudinal imaging of intratumoral distributions of antibodies in vivo in mouse cancer models is of great importance for developing cancer therapies. In this study, multipinhole SPECT with sub-half-millimeter resolution was tested for exploring intratumoral distributions of radiolabeled antibodies directed toward the epidermal growth factor receptor (EGFr) and compared with full 3-dimensional target expression assessed by immunohistochemistry. METHODS: (111)In-labeled zalutumumab, a human monoclonal human EGFr-targeting antibody, was administered at a nonsaturating dose to 3 mice with xenografted A431 tumors exhibiting high EGFr expression. Total-body and focused in vivo tumor SPECT was performed at 0 and 48 h after injection and compared both visually and quantitatively with full 3-dimensional immunohistochemical staining for EGFr target expression. RESULTS: SPECT at 48 h after injection showed that activity was predominantly concentrated in the tumor (10.5% ± 1.3% of the total-body activity; average concentration, 30.1% ± 4.6% of the injected dose per cubic centimeter). (111)In-labeled EGFr-targeting antibodies were distributed heterogeneously throughout the tumor. Some hot spots were observed near the tumor rim. Immunohistochemistry indicated that the antibody distributions obtained by SPECT were morphologically similar to those obtained for ex vivo EGFr target expression. Regions showing low SPECT activity were necrotic or virtually negative for EGFr target expression. A good correlation (r = 0.86, P < 0.0001) was found between the percentage of regions showing low activity on SPECT and the percentage of necrotic tissue on immunohistochemistry. CONCLUSION: Multipinhole SPECT enables high-resolution visualization and quantification of the heterogeneity of (111)In-zalutumumab concentrations in vivo.

Murine cardiac images obtained with focusing pinhole SPECT are barely influenced by extra-cardiac activity.

Ultra-high-resolution SPECT images can be obtained with focused multipinhole collimators. Here we investigate the influence of unwanted high tracer uptake outside the scan volume on reconstructed tracer distributions inside the scan volume, for (99m)Tc-tetrofosmin myocardial perfusion scanning in mice. Simulated projections of a digital mouse phantom (MOBY) in a focusing multipinhole SPECT system (U-SPECT-II, MILabs, The Netherlands) were generated. With this system differently sized user-defined scan volumes can be selected, by translating the animal in 3D through the focusing collimators. Scan volume selections were set to (i) a minimal volume containing just the heart, acquired without translating the animal during scanning, (ii) a slightly larger scan volume as is typically applied for the heart, requiring only small XYZ translations during scanning, (iii) same as (ii), but extended further transaxially, and (iv) same as (ii), but extended transaxially to cover the full thorax width (gold standard). Despite an overall negative bias that is significant for the minimal scan volume, all selected volumes resulted in visually similar images. Quantitative differences in the reconstructed myocardium between gold standard and the results from the smaller scan volume selections were small; the 17 standardized myocardial segments of a bull's eye plot, normalized to the myocardial mean of the gold standard, deviated on average 6.0%, 2.5% and 1.9% for respectively the minimal, the typical and the extended scan volume, while maximum absolute deviations were respectively 18.6%, 9.0% and 5.2%. Averaged over ten low-count noisy simulations, the mean absolute deviations were respectively 7.9%, 3.2% and 1.9%. In low-count noisy simulations, the mean and maximum absolute deviations for the minimal scan volume could be reduced to respectively 4.2% and 12.5% by performing a short survey scan of the exterior activity and focusing the remaining scan time at the organ of interest. We conclude that reconstructed tracer distribution in the myocardium can be influenced by activity in surrounding organs when a too narrow scan volume is used. With slightly larger scan volumes this problem is adequately suppressed. This approach produced a smaller mean deviation and may be more effective than employing a narrow scan volume with an additional survey scan.

Pixel-based subsets for rapid multi-pinhole SPECT reconstruction.

Block-iterative image reconstruction methods, such as ordered subset expectation maximization (OSEM), are commonly used to accelerate image reconstruction. In OSEM, the speed-up factor over maximum likelihood expectation maximization (MLEM) is approximately equal to the number of subsets in which the projection data are divided. Traditionally, each subset consists of a couple of projection views, and the more subsets are used, the more the solution deviates from MLEM solutions. We found for multi-pinhole single photon emission computed tomography (SPECT) that even moderate acceleration factors in OSEM lead to inaccurate reconstructions. Therefore, we introduce pixel-based ordered subset expectation maximization (POSEM), which is based on an alternative subset choice. Pixels in each subset are spread out regularly over projections and are spatially separated as much as possible. We validated POSEM for data acquired with a focusing multi-pinhole SPECT system. Performance was compared with traditional OSEM and MLEM for a rat total body bone scan, a gated mouse myocardial perfusion scan and a Defrise phantom scan. We found that POSEM can be operated at acceleration factors that are often an order of magnitude higher than in traditional OSEM.