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1.  Computation of the glandular radiation dose in digital tomosynthesis of the breast 
Medical physics  2007;34(1):221-232.
Tomosynthesis of the breast is currently a topic of intense interest as a logical next step in the evolution of digital mammography. This study reports on the computation of glandular radiation dose in digital tomosynthesis of the breast. Previously, glandular dose estimations in tomosynthesis have been performed using data from studies of radiation dose in conventional planar mammography. This study evaluates, using Monte Carlo methods, the normalized glandular dose (DgN) to the breast during a tomosynthesis study, and characterizes its dependence on breast size, tissue composition, and x-ray spectrum. The conditions during digital tomosynthesis imaging of the breast were simulated using a computer program based on the Geant4 toolkit. With the use of simulated breasts of varying size, thickness and tissue composition, the DgN to the breast tissue was computed for varying x-ray spectra and tomosynthesis projection angle. Tomosynthesis projections centered about both the cranio-caudal (CC) and medio-lateral oblique (MLO) views were simulated. For each projection angle, the ratio of the glandular dose for that projection to the glandular dose for the zero degree projection was computed. This ratio was denoted the relative glandular dose (RGD) coefficient, and its variation under different imaging parameters was analyzed. Within mammographic energies, the RGD was found to have a weak dependence on glandular fraction and x-ray spectrum for both views. A substantial dependence on breast size and thickness was found for the MLO view, and to a lesser extent for the CC view. Although RGD values deviate substantially from unity as a function of projection angle, the RGD averaged over all projections in a complete tomosynthesis study varies from 0.91 to 1.01. The RGD results were fit to mathematical functions and the resulting equations are provided.
PMCID: PMC4280100  PMID: 17278508
tomosynthesis; digital mammography; dosimetry; breast; Monte Carlo
2.  Solid-state fluoroscopic imager for high-resolution angiography: Parallel-cascaded linear systems analysis 
Medical physics  2004;31(5):1258-1268.
Cascaded linear systems based modeling techniques have been used in the past to predict important system parameters that have a direct impact on image quality. Such models are also useful in optimizing system parameters to improve image quality. In this work, detailed analysis of a solid-state fluoroscopic imaging system intended for high-resolution angiography is presented with the use of such a model. The imaging system analyzed through this model uses four 8×8 cm three-side buttable interlined charge-coupled devices (CCDs) specifically designed for high-resolution angiography and tiled in a seamless fashion to achieve a field of view (FOV) of 16×16 cm. Larger FOVs can be achieved by tiling more CCDs in a similar manner. The system employs a CsI:Tl scintillator coupled to the CCDs by straight (nontapering) fiberoptics and can potentially be operated in 78, 156, or 234 μm pixel pitch modes. The system parameters analyzed through this model include presampling modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE). The results of the simulations performed indicate that DQE(0) in excess of 0.6 is achievable, with the imager operating at 156 μm pixel pitch, 30 frames/s, and employing a 450-μm-thick CsI:Tl scintillator, even at a low fluoroscopic exposure rate of 1 μR/frame. Further, at a nominal fluoroscopic exposure rate of 2.5 μR/frame there was no noticeable degradation of the DQE even at the 78 μm pixel pitch mode suggesting that it is feasible to perform high-resolution angiography hitherto unattainable in clinical practice.
PMCID: PMC4280104  PMID: 15191318
fluoroscopy; angiography; charge-coupled devices; cascaded linear systems analysis; detective quantum efficiency (DQE)
3.  Mammographic imaging with a small format CCD-based digital cassette: Physical characteristics of a clinical systema 
Medical physics  2000;27(8):1832-1840.
The physical characteristics of a clinical charge coupled device (CCD)-based imager (Senovision, GE Medical Systems, Milwaukee, WI) for small-field digital mammography have been investigated. The imager employs a MinR 2000™ (Eastman Kodak Company, Rochester, NY) scintillator coupled by a 1:1 optical fiber to a front-illuminated 61×61 mm CCD operating at a pixel pitch of 30 microns. Objective criteria such as modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), and noise equivalent quanta (NEQ) were employed for this evaluation. The results demonstrated a limiting spatial resolution (10% MTF) of 10 cy/mm. The measured DQE of the current prototype utilizing a 28 kVp, Mo–Mo spectrum beam hardened with 4.5 cm Lucite is ~40% at close to zero spatial frequency at an exposure of 8.2 mR, and decreases to ~28% at a low exposure of 1.1 mR. Detector element nonuniformity and electronic gain variations were not significant after appropriate calibration and software corrections. The response of the imager was linear and did not exhibit signal saturation under tested exposure conditions.
PMCID: PMC4280185  PMID: 10984230
breast imaging; digital mammography; physics; image quality; detective quantum efficiency (DQE)
4.  Solid-state fluoroscopic imager for high-resolution angiography: Physical characteristics of an 8 cm×8 cm experimental prototype 
Medical physics  2004;31(6):1462-1472.
In this paper, the performance of an 8 cm×8 cm three-side buttable charge-coupled device (CCD)-based imager specially designed for high-resolution fluoroscopy and operating in fluoroscopic (30 frames/second) mode is presented in terms of the presampling modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE). The 8 cm×8 cm CCD imager is coupled to a 450 μm thick CsI:Tl scintillator by nondemagnifying (straight, 1:1) fiberoptics. The CCD imager has a fundamental pixel pitch of 39 μm and incorporates an optically opaque interline (data) channel. The CCD imager was operated at 156 μm pixel pitch by binning 4×4 adjacent pixels prior to readout. The fluoroscopic image lag was measured and accounted for in the DQE estimate to provide lag-corrected DQE. The measured limiting spatial resolution at 10% presampling MTF with the imager operated at 156 μm pixel pitch (Nyquist sampling limit: 3.21 cy/mm) was 3.6 cy/mm. In the pulsed fluoroscopic mode, the first-frame image lag was less than 0.9%. The lag-corrected DQE(0) of ~0.62 was achieved even at a low fluoroscopic exposure rate of 1 μR/frame. Grid phantom measurements indicate no appreciable distortion. Results from DQE and image lag measurements at fluoroscopic exposure rates combined with the high spatial resolution observed from the MTF suggest that this type of imager or its variants may be a potential candidate for high-resolution neuro-interventional imaging, cardiovascular imaging, pediatric angiography, and small animal imaging. Since the CCD is three-side buttable, four such CCD modules can be joined to form a 2×2 matrix providing a field of view of 16 cm×16 cm.
PMCID: PMC4280188  PMID: 15259649
fluoroscopy; angiography; charge-coupled devices (CCD); presampling modulation transfer function (MTF); detective quantum efficiency (DQE)
5.  Full breast digital mammography with an amorphous silicon-based flat panel detector: Physical characteristics of a clinical prototype 
Medical physics  2000;27(3):558-567.
The physical characteristics of a clinical prototype amorphous silicon-based flat panel imager for full-breast digital mammography have been investigated. The imager employs a thin thallium doped CsI scintillator on an amorphous silicon matrix of detector elements with a pixel pitch of 100 μm. Objective criteria such as modulation transfer function (MTF), noise power spectrum, detective quantum efficiency (DQE), and noise equivalent quanta were employed for this evaluation. The presampling MTF was found to be 0.73, 0.42, and 0.28 at 2, 4, and 5 cycles/mm, respectively. The measured DQE of the current prototype utilizing a 28 kVp, Mo–Mo spectrum beam hardened with 4.5 cm Lucite is ~55% at close to zero spatial frequency at an exposure of 32.8 mR, and decreases to ~40% at a low exposure of 1.3 mR. Detector element nonuniformity and electronic gain variations were not significant after appropriate calibration and software corrections. The response of the imager was linear and did not exhibit signal saturation under tested exposure conditions.
PMCID: PMC4280189  PMID: 10757607
breast imaging; digital mammography; physics; image quality; detective quantum efficiency (DQE)
6.  Scatter radiation in digital tomosynthesis of the breast 
Medical physics  2007;34(2):564-576.
Digital tomosynthesis of the breast is being investigated as one possible solution to the problem of tissue superposition present in planar mammography. This imaging technique presents various advantages that would make it a feasible replacement for planar mammography, among them similar, if not lower, radiation glandular dose to the breast; implementation on conventional digital mammography technology via relatively simple modifications; and fast acquisition time. One significant problem that tomosynthesis of the breast must overcome, however, is the reduction of x-ray scatter inclusion in the projection images. In tomosynthesis, due to the projection geometry and radiation dose considerations, the use of an antiscatter grid presents several challenges. Therefore, the use of postacquisition software-based scatter reduction algorithms seems well justified, requiring a comprehensive evaluation of x-ray scatter content in the tomosynthesis projections. This study aims to gain insight into the behavior of x-ray scatter in tomosynthesis by characterizing the scatter point spread functions (PSFs) and the scatter to primary ratio (SPR) maps found in tomosynthesis of the breast. This characterization was performed using Monte Carlo simulations, based on the Geant4 toolkit, that simulate the conditions present in a digital tomosynthesis system, including the simulation of the compressed breast in both the cranio-caudal (CC) and the medio-lateral oblique (MLO) views. The variation of the scatter PSF with varying tomosynthesis projection angle, as well as the effects of varying breast glandular fraction and x-ray spectrum, was analyzed. The behavior of the SPR for different projection angle, breast size, thickness, glandular fraction, and x-ray spectrum was also analyzed, and computer fit equations for the magnitude of the SPR at the center of mass for both the CC and the MLO views were found. Within mammographic energies, the x-ray spectrum was found to have no appreciable effect on the scatter PSF and on the SPR. Glandular fraction and compressed breast size were found to have a small effect, while compressed breast thickness and projection angle, as expected, introduced large variations in both the scatter PSF and SPR. The presence of the breast support plate and the detector cover plate in the simulations introduced important effects on the SPR, which are also relevant to the scatter content in planar mammography.
PMCID: PMC4280187  PMID: 17388174
tomosynthesis; digital mammography; scatter; breast; Monte Carlo
7.  Automated Lung Segmentation of Diseased and Artifact-Corrupted MR Sections 
Medical physics  2006;33(9):3085-3093.
Segmentation of the lungs within magnetic resonance (MR) scans is a necessary step in the computer-based analysis of thoracic MR images. This process is often confounded by image acquisition artifacts and disease-induced morphological deformation. We have developed an automated method for lung segmentation that is insensitive to these complications. The automated method was applied to 23 thoracic MR scans (413 sections) obtained from 10 patients. Two radiologists manually outlined the lung regions in a random sample of 101 sections (n=202 lungs), and the extent to which disease or artifact confounded lung border visualization was evaluated. Accuracy of lung regions extracted by the automated segmentation method was quantified by comparison with the radiologist-defined lung regions using an area overlap measure (AOM) that ranged from 0 (disjoint lung regions) to 1 (complete overlap). The AOM between each observer and the automated method was 0.82 when averaged over all lungs. The average AOM in the lung bases, where lung segmentation is most difficult, was 0.73.
PMCID: PMC3985425  PMID: 17022200
segmentation; magnetic resonance imaging (MRI); image processing; cardiac motion artifact; pulmonary motion artifact; computer-aided diagnosis (CAD)
8.  Magnetically-assisted remote control (MARC) steering of endovascular catheters for interventional MRI: An equation for predicting deflection and experimental validation 
Medical physics  2007;34(8):3135-3142.
Direct current applied to wire coils wound at the tip of an endovascular catheter can be used to remotely steer a catheter under magnetic resonance imaging guidance. In this study, we derive and validate an equation that characterizes the relationship between the number of solenoid turns, applied current, catheter stiffness, magnetic field strength, and resulting catheter tip deflections.
Method and Materials
Solenoids of 50, 100, 150 turns were wound on separate 1.8F and 5F catheters. Varying currents were applied using a DC power supply in the MRI control room. Images were obtained with a 1.5 T or a 3 T MR scanner with the distal catheter suspended in the main scanner magnetic field in a water bath on the scanner bed. ssFSE and FIESTA fast imaging sequences were used. Deflection angles were measured on acquired sagittal images using eFilm software.
Relationships between variables predicted by the derived equation, θ/sin(γ−θ) = nIAB/kθ, where θ is the deflection angle, n is the number of solenoidal turns, I is the current, A is the cross-sectional area of the catheter tip, B is the MR scanner main magnetic field, kθ is related to the catheter elastic modulus, and γ is the initial angle between the catheter tip and B, were observed (R2 = 0.935–0.987).
An equation that predicts catheter tip deflection has been derived and validated experimentally for MARC-steering of endovascular catheters in interventional MRI. Consequent accurate prediction of catheter tip behavior using this novel mechanism will enhance control of the endovascular catheter tip, as well as decrease the risk of procedural complications such as dissection and embolus formation.
PMCID: PMC3980585  PMID: 17879774
interventional radiology; MRI; catheter; catheterization; vascular disease
9.  Second Cancer Incidence Risk Estimates using BEIR VII Models for Standard and Complex External Beam Radiotherapy for Early Breast Cancer 
Medical physics  2012;39(10):5814-5824.
To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy including cone beam CT verification following breast conservation surgery for early breast cancer.
Doses from breast radiotherapy and kilovoltage cone beam CT (CBCT) exposures were obtained from thermoluminescent dosimeter (TLD) measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated : (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) non-coplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, (v) inverse-planned three volume SIB. Conformal and intensity modulated radiotherapy (IMRT) methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low local cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contra-lateral breast, left and right lung, oesophagus, stomach, liver, colon and bladder. Biological Effects of Ionising Radiation (BEIR) VII cancer incidence models were applied to the measured mean organ doses to determine Lifetime Attributable Risk (LAR) for ages at exposure from 35 to 80 years according to radiotherapy techniques, and included dose from the CBCT imaging.
All LAR decreased with age at exposure and were lowest for brain, thyroid, liver and bladder (< 0.1%). There was little dependence of LAR on radiotherapy technique for these organs and for colon and stomach. LAR values for the lungs for the three SIB techniques were two to three times those from WBRT and APBI. Uncertainties in the LAR models outweigh any differences in lung LAR between the SIB methods. Constraints in the planning of the SIB methods ensured that contra-lateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose.
Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy ; this is outweighed by the threefold reduction in 5 year local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favourable impact on risk of second cancer in the contra-lateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRT increased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models’ uncertainties.
PMCID: PMC3498624  PMID: 23039620
second cancer incidence; breast radiotherapy; image-guided radiotherapy; partial breast
10.  Quantitative error analysis for computer assisted navigation: a feasibility study 
Medical physics  2013;40(2):021910.
The benefit of computer-assisted navigation depends on the registration process, at which patient features are correlated to some preoperative imagery. The operator-induced uncertainty in localizing patient features – the User Localization Error (ULE) - is unknown and most likely dominating the application accuracy. This initial feasibility study aims at providing first data for ULE with a research navigation system.
Active optical navigation was done in CT-images of a plastic skull, an anatomic specimen (both with implanted fiducials) and a volunteer with anatomical landmarks exclusively. Each object was registered ten times with 3, 5, 7, and 9 registration points. Measurements were taken at 10 (anatomic specimen and volunteer) and 11 targets (plastic skull). The active NDI Polaris system was used under ideal working conditions (tracking accuracy 0.23 mm root mean square, RMS; probe tip calibration was 0.18 mm RMS. Variances of tracking along the principal directions were measured as 0.18 mm2, 0.32 mm2, and 0.42 mm2. ULE was calculated from predicted application accuracy with isotropic and anisotropic models and from experimental variances, respectively.
The ULE was determined from the variances as 0.45 mm (plastic skull), 0.60 mm (anatomic specimen), and 4.96 mm (volunteer). The predicted application accuracy did not yield consistent values for the ULE.
Quantitative data of application accuracy could be tested against prediction models with iso- and anisotropic noise models and revealed some discrepancies. This could potentially be due to the facts that navigation and one prediction model wrongly assume isotropic noise (tracking is anisotropic), while the anisotropic noise prediction model assumes an anisotropic registration strategy (registration is isotropic in typical navigation systems). The ULE data are presumably the first quantitative values for the precision of localizing anatomical landmarks and implanted fiducials. Submillimetric localization is possible for implanted screws; anatomic landmarks are not suitable for high-precision clinical navigation.
PMCID: PMC3700679  PMID: 23387758
application accuracy; navigation; human localization error; registration
11.  Study of the performance of a novel 1 mm resolution dual-panel PET camera design dedicated to breast cancer imaging using Monte Carlo simulation 
Medical physics  2007;34(2):689-702.
We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The PET camera under development has two 10 × 15 cm2 plates that are constructed from arrays of 1 × 1 × 3 mm3 LSO crystals coupled to novel ultra-thin (<200 μm) silicon position-sensitive avalanche photodiodes (PSAPD). In this design the photodetectors are configured “edge-on” with respect to incoming photons which encounter a minimum of 2 cm thick of LSO with directly measured photon interaction depth. Simulations predict that this camera will have 10–15% photon sensitivity, for an 8–4 cm panel separation. Detector measurements show ~1 mm3 intrinsic spatial resolution, <12% energy resolution, and ~2 ns coincidence time resolution. By performing simulated dual-panel PET studies using a phantom comprising active breast, heart, and torso tissue, count performance was studied as a function of coincident time and energy windows. We also studied visualization of hot spheres of 2.5–4.0 mm diameter and various locations within the simulated breast tissue for 1 × 1 × 3 mm3, 2 × 2 × 10 mm3, 3 × 3 × 30 mm3, and 4 × 4 × 20 mm3 LSO crystal resolutions and different panel separations. Images were reconstructed by focal plane tomography with attenuation and normalization corrections applied. Simulation results indicate that with an activity concentration ratio of tumor:breast:heart:torso of 10:1:10:1 and 30 s of acquisition time, only the dual-plate PET camera comprising 1 × 1 × 3 mm3 crystals could resolve 2.5 mm diameter spheres with an average peak-to-valley ratio of 1.3.
PMCID: PMC3696388  PMID: 17388187
12.  MR-guided adaptive focusing of therapeutic ultrasound beams in the human head 
Medical Physics  2012;39(2):1141.
This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) in the framework of non-invasive transcranial High Intensity Focused Ultrasound (HIFU) therapy.
Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. We evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical Magnetic Resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A non-iterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head.
The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation based on X-ray computed tomography (CT) scans.
The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications.
PMCID: PMC3432021  PMID: 22320825
MRI; adaptive focusing; MR-ARFI; ultrasound transcranial therapy; HIFU
13.  Radiative transport in the delta-P1 approximation for semi-infinite turbid media 
Medical physics  2008;35(2):681-693.
We have developed an analytic solution for spatially resolved diffuse reflectance within the δ-P1 approximation to the radiative transport equation for a semi-infinite homogeneous turbid medium. We evaluate the performance of this solution by comparing its predictions with those provided by Monte Carlo simulations and the standard diffusion approximation. We demonstrate that the δ-P1 approximation provides accurate estimates for spatially resolved diffuse reflectance in both low and high scattering media. We also develop a multi-stage nonlinear optimization algorithm in which the radiative transport estimates provided by the δ-P1 approximation are used to recover the optical absorption (μa), reduced scattering ( μs′), and single-scattering asymmetry coefficients (g1) of liquid and solid phantoms from experimental measurements of spatially resolved diffuse reflectance. Specifically, the δ-P1 approximation can be used to recover μa, μs′, and g1 with errors within ±22%, ±18%, and ±17%, respectively, for both intralipid-based and siloxane-based tissue phantoms. These phantoms span the optical property range 4<(μs′/μa)<117. Using these same measurements, application of the standard diffusion approximation resulted in the recovery of μa and μs′ with errors of ±29% and ±25%, respectively. Collectively, these results demonstrate that the δ-P1 approximation provides accurate radiative transport estimates that can be used to determine accurately the optical properties of biological tissues, particularly in spectral regions where tissue may display moderate/low ratios of reduced scattering to absorption ( μs′/μa).
PMCID: PMC3509770  PMID: 18383690
14.  Evaluation of a 3D local multiresolution algorithm for the correction of partial volume effects in positron emission tomography 
Medical Physics  2011;38(9):4920-4923.
Partial volume effects (PVE) are consequences of the limited spatial resolution in emission tomography leading to under-estimation of uptake in tissues of size similar to the point spread function (PSF) of the scanner as well as activity spillover between adjacent structures. Among PVE correction methodologies, a voxel-wise mutual multi-resolution analysis (MMA) was recently introduced. MMA is based on the extraction and transformation of high resolution details from an anatomical image (MR/CT) and their subsequent incorporation into a low resolution PET image using wavelet decompositions. Although this method allows creating PVE corrected images, it is based on a 2D global correlation model which may introduce artefacts in regions where no significant correlation exists between anatomical and functional details.
A new model was designed to overcome these two issues (2D only and global correlation) using a 3D wavelet decomposition process combined with a local analysis. The algorithm was evaluated on synthetic, simulated and patient images, and its performance was compared to the original approach as well as the geometric transfer matrix (GTM) method.
Quantitative performance was similar to the 2D global model and GTM in correlated cases. In cases where mismatches between anatomical and functional information were present the new model outperformed the 2D global approach, avoiding artefacts and significantly improving quality of the corrected images and their quantitative accuracy.
A new 3D local model was proposed for a voxel-wise PVE correction based on the original mutual multi-resolution analysis approach. Its evaluation demonstrated an improved and more robust qualitative and quantitative accuracy compared to the original MMA methodology, particularly in the absence of full correlation between anatomical and functional information.
PMCID: PMC3485215  PMID: 21978037
Algorithms; Artifacts; Brain; radionuclide imaging; Humans; Imaging, Three-Dimensional; methods; Linear Models; Positron-Emission Tomography; methods; Reproducibility of Results; Whole Body Imaging; emission tomography; partial volume effects; resolution and intensity recovery; wavelet transform; multi-modality
15.  Technical note: Correlation of respiratory motion between external patient surface and internal anatomical landmarks 
Medical Physics  2011;38(6):3157-3164.
Current respiratory motion monitoring devices used for motion synchronization in medical imaging and radiotherapy provide either 1D respiratory signals over a specific region or 3D information based on few external or internal markers. On the other hand, newer technology may offer the potential to monitor the entire patient external surface in real time. The main objective of this study was to assess the motion correlation between such an external patient surface and internal anatomical landmarks motion.
Four dimensional Computed Tomography (4D CT) volumes for ten patients were used in this study. Anatomical landmarks were manually selected in the thoracic region across the 4D CT datasets by two experts. The landmarks included normal structures as well as the tumour location. In addition, a distance map representing the entire external patient surface, which corresponds to surfaces acquired by a Time of Flight (ToF) camera or similar devices, was created by segmenting the skin of all 4D CT volumes using a thresholding algorithm. Finally, the correlation between the internal landmarks and external surface motion was evaluated for different regions (placement and size) throughout a patient’s surface.
Significant variability was observed in the motion of the different parts of the external patient surface. The larger motion magnitude was consistently measured in the central regions of the abdominal and the thoracic areas for the different patient datasets considered. The highest correlation coefficients were observed between the motion of these external surface areas and internal landmarks such as the diaphragm and mediastinum structures as well as the tumour location landmarks (0.8 ± 0.18 and 0.72 ± 0.12 for the abdominal and the thoracic regions respectively). Worse correlation was observed when one considered landmarks not significantly influenced by respiratory motion such as the apex and the sternum.
Discussion and conclusions
There were large differences in the motion correlation observed considering different regions of interest placed over a patients’ external surface and internal anatomical landmarks. The positioning of current devices used for respiratory motion synchronization may reduce such correlation by averaging the motion over correlated and poorly correlated external regions. The potential of capturing in real-time the motion of the complete external patient surface as well as choosing the area of the surface that correlates best with the internal motion should allow reducing such variability and associated errors in both respiratory motion synchronization and subsequent motion modeling processes.
PMCID: PMC3379968  PMID: 21815390
Fiducial Markers; Four-Dimensional Computed Tomography; standards; Humans; Movement; Respiration; respiratory motion; patient external surface; 4D CT
16.  On the potential of ultrasound elastography for pressure ulcer early detection 
Medical Physics  2011;38(4):1943-1950.
Pressure ulcers are areas of soft tissue breakdown induced by a sustained mechanical stress that damages the skin and underlying tissues. They represent a considerable burden to the society in terms of health care and cost. Yet, techniques for prevention and detection of pressure ulcers still remain very limited. In this article, the authors investigated the potential of ultrasound elastography for pressure ulcer early detection. Elastography is an imaging technique providing local information on biological tissue mechanical properties. It is relevant for pressure ulcer detection as this pathology is associated with a gradual stiffening of damaged tissues, beginning in the deeper tissues and progressing toward the skin surface.
A 2D ultrasound elastography method was proposed and its ability in terms of pressure ulcer detection was validated through numerical simulations and physical acquisitions on pressure ulcer mimicking phantoms. In vivo experiments on a rat model are also reported. A maintained pressure was applied on the animal thigh, with a view to generate a pressure ulcer, and ultrasound data were acquired and processed before and after application of this pressure.
Numerical simulations demonstrated that a pressure ulcer can theoretically be detected at a very early stage with ultrasound elastography. Even when the ulcer region was characterized by a low stiffening (ratio of 1.8 relative to normal tissues), the corresponding elastogram clearly underlined the pathological area. This observation was confirmed by the results obtained on a physical phantom mimicking a pressure ulcer at an early stage. Computed elastograms showed strain differences between areas mimicking healthy and pathological tissues. Results corresponding to in vivo experiments revealed a difference in the way tissues behaved before and after the pressure was applied on the animal thigh, which strongly suggests the presence of a pathological area.
Experiments demonstrated that ultrasound elastography is a promising technique for pressure ulcer detection, especially at an early stage of the pathology, when the disease is still visually undetectable. In the absence of any gold standard method, this is also a first step toward the development of a quantitative technique.
PMCID: PMC3337043  PMID: 21626927
pressure ulcer; ultrasound; elastography; medical imaging
17.  Validation for 2D/3D registration I: A new gold standard data set 
Medical physics  2011;38(3):1481-1490.
In this article, the authors propose a new gold standard data set for the validation of two-dimensional/three-dimensional (2D/3D) and 3D/3D image registration algorithms.
A gold standard data set was produced using a fresh cadaver pig head with attached fiducial markers. The authors used several imaging modalities common in diagnostic imaging or radiotherapy, which include 64-slice computed tomography (CT), magnetic resonance imaging using Tl, T2, and proton density sequences, and cone beam CT imaging data. Radiographic data were acquired using kilovoltage and megavoltage imaging techniques. The image information reflects both anatomy and reliable fiducial marker information and improves over existing data sets by the level of anatomical detail, image data quality, and soft-tissue content. The markers on the 3D and 2D image data were segmented using analyze 10.0 (AnalyzeDirect, Inc., Kansas City, KN) and an in-house software.
The projection distance errors and the expected target registration errors over all the image data sets were found to be less than 2.71 and 1.88 mm, respectively.
The gold standard data set, obtained with state-of-the-art imaging technology, has the potential to improve the validation of 2D/3D and 3D/3D registration algorithms for image guided therapy.
PMCID: PMC3091017  PMID: 21520860
gold standard; image registration; image guidance; radiotherapy
18.  Validation for 2D/3D registration II: The comparison of intensity- and gradient-based merit functions using a new gold standard data set 
Medical physics  2011;38(3):1491-1502.
A new gold standard data set for validation of 2D/3D registration based on a porcine cadaver head with attached fiducial markers was presented in the first part of this article. The advantage of this new phantom is the large amount of soft tissue, which simulates realistic conditions for registration. This article tests the performance of intensity- and gradient-based algorithms for 2D/3D registration using the new phantom data set.
Intensity-based methods with four merit functions, namely, cross correlation, rank correlation, correlation ratio, and mutual information (MI), and two gradient-based algorithms, the backprojection gradient-based (BGB) registration method and the reconstruction gradient-based (RGB) registration method, were compared. Four volumes consisting of CBCT with two fields of view, 64 slice multidetector CT, and magnetic resonance-T1 weighted images were registered to a pair of kV x-ray images and a pair of MV images. A standardized evaluation methodology was employed. Targets were evenly spread over the volumes and 250 starting positions of the 3D volumes with initial displacements of up to 25 mm from the gold standard position were calculated. After the registration, the displacement from the gold standard was retrieved and the root mean square (RMS), mean, and standard deviation mean target registration errors (mTREs) over 250 registrations were derived. Additionally, the following merit properties were computed: Accuracy, capture range, number of minima, risk of nonconvergence, and distinctiveness of optimum for better comparison of the robustness of each merit.
Among the merit functions used for the intensity-based method, MI reached the best accuracy with an RMS mTRE down to 1.30 mm. Furthermore, it was the only merit function that could accurately register the CT to the kV x rays with the presence of tissue deformation. As for the gradient-based methods, BGB and RGB methods achieved subvoxel accuracy (RMS mTRE down to 0.56 and 0.70 mm, respectively). Overall, gradient-based similarity measures were found to be substantially more accurate than intensity-based methods and could cope with soft tissue deformation and enabled also accurate registrations of the MR-T1 volume to the kV x-ray image.
In this article, the authors demonstrate the usefulness of a new phantom image data set for the evaluation of 2D/3D registration methods, which featured soft tissue deformation. The author’s evaluation shows that gradient-based methods are more accurate than intensity-based methods, especially when soft tissue deformation is present. However, the current nonoptimized implementations make them prohibitively slow for practical applications. On the other hand, the speed of the intensity-based method renders these more suitable for clinical use, while the accuracy is still competitive.
PMCID: PMC3089767  PMID: 21520861
2D/3D registration; image-guided therapy; gradient; intensity; rendering; ray-casting
19.  Proliferation and the advantage of longer-lived radionuclides in radioimmunotherapy 
Medical physics  1998;25(1):37-42.
In our previous study we used the linear-quadratic model [J. Nucl. Med. 35, 1861 (1994)] to confirm our initial finding, based on the time-dose-fractionation model [J. Nucl. Med. 34, 1801 (1993)], that longer-lived radionuclides (e.g., 32P, 91Y) can offer a substantial therapeutic advantage over the shorter-lived radionuclides presently used in radioimmunotherapy (e.g., 90Y). The original calculations using the linear-quadratic (LQ) model did not account for proliferation of the tumor and critical bone marrow tissues. It has been suggested that inclusion of a proliferation term in the LQ model can have a substantial impact on the biologically effective dose (BED). With this in mind, we have reexamined the therapeutic efficacy of longer versus short-lived radionuclides using the LQ model replete with proliferation terms for tumor and bone marrow. Relative advantage factors (RAF), which quantify the overall therapeutic advantage of a long-lived compared to short-lived radionuclide, were calculated accordingly. While the extrapolated initial dose rate required to achieve a given BED can be affected by the inclusion of proliferation terms for both the tumor and marrow, the relative advantage factors for the longer-lived radionuclides were not significantly affected. Longer-lived radionuclides such as 114mIn and 91Y are about three times more therapeutically effective than the shorter-lived 90Y which is currently used in RIT. In other words, for a given therapeutic effect in the tumor, a longer-lived radionuclide can result in a lower deleterious effect to the bone marrow than a short-lived radionuclide. Given that bone marrow is generally considered to be the dose-limiting organ, these results have important implications for radioimmunotherapy.
PMCID: PMC3046635  PMID: 9472824
linear-quadratic model; radioimmunotherapy; dosimetry; proliferation
20.  Joint two-view information for computerized detection of microcalcifications on mammograms 
Medical physics  2006;33(7):2574-2585.
We are developing new techniques to improve the accuracy of computerized microcalcification detection by using the joint two-view information on craniocaudal (CC) and mediolateral-oblique (MLO) views. After cluster candidates were detected using a single-view detection technique, candidates on CC and MLO views were paired using their radial distances from the nipple. Candidate pairs were classified with a similarity classifier that used the joint information from both views. Each cluster candidate was also characterized by its single-view features. The outputs of the similarity classifier and the single-view classifier were fused and the cluster candidate was classified as a true microcalcification cluster or a false-positive (FP) using the fused two-view information. A data set of 116 pairs of mammograms containing microcalcification clusters and 203 pairs of normal images from the University of South Florida (USF) public database was used for training the two-view detection algorithm. The trained method was tested on an independent test set of 167 pairs of mammograms, which contained 71 normal pairs and 96 pairs with microcalcification clusters collected at the University of Michigan (UM). The similarity classifier had a very low FP rate for the test set at low and medium levels of sensitivity. However, the highest mammogram-based sensitivity that could be reached by the similarity classifier was 69%. The single-view classifier had a higher FP rate compared to the similarity classifier, but it could reach a maximum mammogram-based sensitivity of 93%. The fusion method combined the scores of these two classifiers so that the number of FPs was substantially reduced at relatively low and medium sensitivities, and a relatively high maximum sensitivity was maintained. For the malignant microcalcification clusters, at a mammogram-based sensitivity of 80%, the FP rates were 0.18 and 0.35 with the two-view fusion and single-view detection methods, respectively. When the training and test sets were switched, a similar improvement was obtained, except that both the fusion and single-view detection methods had superior test performances on the USF data set than those on the UM data set. Our results indicate that correspondence of cluster candidates on two different views provides valuable additional information for distinguishing FPs from true microcalcification clusters.
PMCID: PMC3026322  PMID: 16898462
computer-aided diagnosis; microcalcification clusters; segmentation
21.  Monte Carlo simulations of dose from microCT imaging procedures in a realistic mouse phantom 
Medical physics  2006;33(1):216-224.
The purpose of this work was to calculate radiation dose and its organ distribution in a realistic mouse phantom from micro-computed tomography (microCT) imaging protocols. CT dose was calculated using GATE and a voxelized, realistic phantom. The x-ray photon energy spectra used in simulations were precalculated with GATE and validated against previously published data. The number of photons required per simulated experiments was determined by direct exposure measurements. Simulated experiments were performed for three types of beams and two types of mouse beds. Dose-volume histograms and dose percentiles were calculated for each organ. For a typical microCT screening examination with a reconstruction voxel size of 200 μm, the average whole body dose varied from 80 mGy (at 80 kVp) to 160 mGy (at 50 kVp), showing a strong dependence on beam hardness. The average dose to the bone marrow is close to the soft tissue average. However, due to dose nonuniformity and higher radiation sensitivity, 5% of the marrow would receive an effective dose about four times higher than the average. If CT is performed longitudinally, a significant radiation dose can be given. The total absorbed radiation dose is a function of milliamperes-second, beam hardness, and desired image quality (resolution, noise and contrast). To reduce dose, it would be advisable to use the hardest beam possible while maintaining an acceptable contrast in the image.
PMCID: PMC3005289  PMID: 16485428
22.  Monte Carlo simulations of absorbed dose in a mouse phantom from 18-fluorine compounds 
Medical physics  2007;34(3):1026-1036.
The purpose of this study was to calculate internal absorbed dose distribution in mice from preclinical small animal PET imaging procedures with fluorine-18 labeled compounds (18FDG, 18FLT, and fluoride ion). The GATE Monte Carlo software and a realistic, voxel-based mouse phantom that included a subcutaneous tumor were used to perform simulations. Discretized time-activity curves obtained from dynamic in vivo studies with each of the compounds were used to set the activity concentration in the simulations. For 18FDG, a realistic range of uptake ratios was considered for the heart and tumor. For each simulated time frame, the biodistribution of the radionuclide in the phantom was considered constant, and a sufficient number of decays were simulated to achieve low statistical uncertainty. Absorbed dose, which was scaled to take into account radioactive decay, integration with time, and changes in biological distribution was reported in mGy per MBq of administered activity for several organs and uptake scenarios. The mean absorbed dose ranged from a few mGy/MBq to hundreds of mGy/MBq. Major organs receive an absorbed dose in a range for which biological effects have been reported. The effects on a given investigation are hard to predict; however, investigators should be aware of potential perturbations especially when the studied organ receives high absorbed dose and when longitudinal imaging protocols are considered.
PMCID: PMC3006169  PMID: 17441249
small animal PET; dosimetry; GATE; Flourine-18
23.  Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry 
Medical physics  2008;35(3):1123-1134.
In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high α/β), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial activity ratio and the S value ratio between the two. In some scenarios, projected BED based on both the cortex and the medulla is a more appropriate constraint on the administered activity than the BED based on the cortex only. Furthermore, different fractionated regimens were considered to reduce renal toxicity. The MIRD-based BED formalism is expected to be useful for patient-specific adjustments of activity and to facilitate the investigation of dose-toxicity correlations with respect to dose-rate and tissue repair mechanism.
PMCID: PMC2974633  PMID: 18404947
dosimetry; radionuclide therapy; biological effective dose
24.  Measurement of the internal diameter of plastic tubes from projection MR images using a model-based least-squares fit approach 
Medical physics  2006;33(6):1643-1653.
Hyperpolarized (HP) 3He MRI is an emerging tool in the diagnosis and evaluation of pulmonary diseases involving bronchoconstriction, such as asthma. Previously, airway diameters from dynamic HP 3He MR images of the lung were assessed manually and subjectively, and were thus prone to uncertainties associated with human error and partial volume effects. A model-based algorithm capable of fully utilizing pixel intensity profile information and attaining subpixel resolution has been developed to measure surrogate airway diameters from HP 3He MR static projection images of plastic tubes. This goal was achieved by fitting ideal pixel intensity profiles for various diameter (6.4 to 19.1 mm) circular tubes to actual pixel intensity data. A phantom was constructed from plastic tubes of various diameters connected in series and filled with water mixed with contrast agent. Projection MR images were then taken of the phantom. The favorable performance of the model-based algorithm compared to manual assessment demonstrates the viability of our approach. The manual and algorithm approaches yielded diameter measurements that generally stayed within 1× the pixel dimension. However, inconsistency of the manual approach can be observed from the larger standard deviations of its measured values. The method was then extended to HP 3He MRI, producing encouraging results at tube diameters characteristic of airways beyond the second generation, thereby justifying their application to lung airway imaging and measurement. Potential obstacles when measuring airway diameters using this method are discussed.
PMCID: PMC2934785  PMID: 16872072
25.  Monte Carlo investigations of megavoltage cone-beam CT using thick, segmented scintillating detectors for soft tissue visualization 
Medical physics  2008;35(1):145-158.
Megavoltage cone-beam computed tomography (MY CBCT) is a highly promising technique for providing volumetric patient position information in the radiation treatment room. Such information has the potential to greatly assist in registering the patient to the planned treatment position, helping to ensure accurate delivery of the high energy therapy beam to the tumor volume while sparing the surrounding normal tissues. Presently, CBCT systems using conventional MV active matrix flat-panel imagers (AMFPIs), which are commonly used in portal imaging, require a relatively large amount of dose to create images that are clinically useful. This is due to the fact that the phosphor screen detector employed in conventional MV AMFPIs utilizes only ~2% of the incident radiation (for a 6 MV x-ray spectrum). Fortunately, thick, segmented scintillating detectors can overcome this limitation, and the first prototype imager has demonstrated highly promising performance for projection imaging at low doses. It is therefore of definite interest to examine the potential performance of such thick, segmented scintillating detectors for MV CBCT. In this study, Monte Carlo simulations of radiation energy deposition were used to examine reconstructed images of cylindrical CT contrast phantoms, embedded with tissue-equivalent objects. The phantoms were scanned at 6 MV using segmented detectors having various design parameters (i.e., detector thickness, as well as scintillator and septal wall materials). Due to constraints imposed by the nature of this study, the size of the phantoms was limited to ~6 cm. For such phantoms, the simulation results suggest that a 40 mm thick, segmented CsI detector with low density septal walls can delineate electron density differences of ~2.3% and 1.3% at doses of 1.54 and 3.08 cGy, respectively. In addition, it was found that segmented detectors with greater thickness, higher density scintillator material, or lower density septal walls exhibit higher contrast-to-noise performance. Finally, the performance of various segmented detectors obtained at a relatively low dose (1.54 cGy) was compared to that of a phosphor screen similar to that employed in conventional MV AMFPIs. This comparison indicates that, for a phosphor screen to achieve the same contrast-to-noise performance as the segmented detectors, ~18 to 59 times more dose is required, depending on the configuration of the segmented detectors.
PMCID: PMC2920060  PMID: 18293571
active matrix flat-panel imager; segmented scintillating detectors; megavoltage cone-beam CT; soft tissue visualization; contrast-to-noise ratio

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