Showing papers in "Physics in Medicine and Biology in 2007"

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

Abstract: The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

Abstract: The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision openended coaxial probe. The tissue composition within the probe’s sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole–Cole model to the complex permittivity data set obtained for each sample and determined median Cole–Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0–30%, 31–84% and 85–100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties. (Some figures in this article are in colour only in the electronic version)

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

Abstract: Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

K-edge imaging in x-ray computed tomography using multi-bin photon counting detectors.

Abstract: After passage through matter, the energy spectrum of a polychromatic beam of x-rays contains valuable information about the elemental composition of the absorber. Conventional x-ray systems or x-ray computed tomography (CT) systems, equipped with scintillator detectors operated in the integrating mode, are largely insensitive to this type of spectral information, since the detector output is proportional to the energy fluence integrated over the whole spectrum. The main purpose of this paper is to investigate to which extent energy-sensitive photon counting devices, operated in the pulse-mode, are capable of revealing quantitative information about the elemental composition of the absorber. We focus on the detection of element-specific, K-edge discontinuities of the photo-electric cross-section. To be specific, we address the question of measuring and imaging the local density of a gadolinium-based contrast agent, in the framework of a generalized dual-energy pre-processing. Our results are very promising and seem to open up new possibilities for the imaging of the distribution of elements with a high atomic number Z in the human body using x-ray attenuation measurements. To demonstrate the usefulness of the detection and the appropriate processing of the spectral information, we present simulated images of an artherosclerotic coronary vessel filled with gadolinium-based contrast agent. While conventional systems, equipped with integrating detectors, often fail to differentiate between contrast filled lumen and artherosclerotic plaque, the use of an energy-selective detection system based on the counting of individual photons reveals a strong contrast between plaque and contrast agent.

Digimouse: a 3D whole body mouse atlas from CT and cryosection data

Abstract: We have constructed a three-dimensional (3D) whole body mouse atlas from coregistered x-ray CT and cryosection data of a normal nude male mouse. High quality PET, x-ray CT and cryosection images were acquired post mortem from a single mouse placed in a stereotactic frame with fiducial markers visible in all three modalities. The image data were coregistered to a common coordinate system using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using interactive editing tools we segmented and labelled whole brain, cerebrum, cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys, testes, bladder, skeleton and skin surface. The final atlas consists of the 3D volume, in which the voxels are labelled to define the anatomical structures listed above, with coregistered PET, x-ray CT and cryosection images. To illustrate use of the atlas we include simulations of 3D bioluminescence and PET image reconstruction. Optical scatter and absorption values are assigned to each organ to simulate realistic photon transport within the animal for bioluminescence imaging. Similarly, 511 keV photon attenuation values are assigned to each structure in the atlas to simulate realistic photon attenuation in PET. The Digimouse atlas and data are available at http://neuroimage.usc.edu/Digimouse.html.

4D MR imaging of respiratory organ motion and its variability

Abstract: This paper describes a method for 4D imaging, which is used to study respiratory organ motion, a key problem in various treatments. Whilst the commonly used imaging methods rely on simplified breathing patterns to acquire one breathing cycle, the proposed method was developed to study irregularities in organ motion during free breathing over tens of minutes. The method does not assume a constant breathing depth or even strict periodicity and does not depend on an external respiratory signal. Time-resolved 3D image sequences were reconstructed by retrospective stacking of dynamic 2D images using internal image-based sorting. The generic method is demonstrated for the liver and for the lung. Quantitative evaluations of the volume consistency show the advantages over one-dimensional measurements for image sorting. Dense deformation fields describing the respiratory motion were estimated from the reconstructed volumes using non-rigid 3D registration. All obtained motion fields showed variations in the range of minutes such as drifts and deformations, which changed both the exhalation position of the liver and the breathing pattern. The obtained motion data are used in proton therapy planning to evaluate dose delivery methodologies with respect to their motion sensitivity. Besides this application, the new possibilities of studying respiratory motion are valuable for other applications such as the evaluation of gating techniques with respect to residual motion.

Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity.

Abstract: MR elastography (MRE) enables the noninvasive determination of the viscoelastic behavior of human internal organs based on their response to oscillatory shear stress. An experiment was developed that combines multifrequency shear wave actuation with broad-band motion sensitization to extend the dynamic range of a single MRE examination. With this strategy, multiple wave images corresponding to different driving frequencies are simultaneously received and can be analyzed by evaluating the dispersion of the complex modulus over frequency. The technique was applied on the brain and liver of five healthy volunteers. Its repeatability was tested by four follow-up studies in each volunteer. Five standard rheological models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed for their ability to reproduce the observed dispersion curves. The three-parameter Zener model was found to yield the most consistent results with two shear moduli mu(1) = 0.84 +/- 0.22 (1.36 +/- 0.31) kPa, mu(2) = 2.03 +/- 0.19 (1.86 +/- 0.34) kPa and one shear viscosity of eta = 6.7 +/- 1.3 (5.5 +/- 1.6) Pa s (interindividual mean +/- SD) in brain (liver) experiments. Significant differences between the rheological parameters of brain and liver were found for mu(1) and eta (P < 0.05), indicating that human brain is softer and possesses a higher viscosity than liver.

Performance evaluation of the ECAT HRRT: an LSO-LYSO double layer high resolution, high sensitivity scanner

Abstract: The ECAT high resolution research tomograph (HRRT) is a dedicated brain and small animal PET scanner, with design features that enable high image spatial resolution combined with high sensitivity. The HRRT is the first commercially available scanner that utilizes a double layer of LSO/LYSO crystals to achieve photon detection with depth-of-interaction information. In this study, the performance of the commercial LSO/LYSO HRRT was characterized, using the NEMA protocol as a guideline. Besides measurement of spatial resolution, energy resolution, sensitivity, scatter fraction, count rate performance, correction for attenuation and scatter, hot spot recovery and image quality, a clinical evaluation was performed by means of a HR+/HRRT human brain comparison study. Point source resolution varied across the field of view from approximately 2.3 to 3.2 mm (FWHM) in the transaxial direction and from 2.5 to 3.4 mm in the axial direction. Absolute line-source sensitivity ranged from 2.5 to 3.3% and the NEMA-2001 scatter fraction equalled 45%. Maximum NECR was 45 kcps and 148 kcps according to the NEMA-2001 and 1994 protocols, respectively. Attenuation and scatter correction led to a volume uniformity of 6.3% and a system uniformity of 3.1%. Reconstructed values deviated up to 15 and 8% in regions with high and low densities, respectively, which can possibly be assigned to inaccuracies in scatter estimation. Hot spot recovery ranged from 60 to 94% for spheres with diameters of 1 to 2.2 cm. A high quantitative agreement was met between HR+ and HRRT clinical data. In conclusion, the ECAT HRRT has excellent resolution and sensitivity properties, which is a crucial advantage in many research studies.

Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration

Abstract: A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO(2)) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO(2) and HHb, total haemoglobin concentration and SO(2). The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of +/-3.8 g l(-1) (+/-58 microM) and +/-4.4 g l(-1) (+/-68 microM) for the HbO(2) and HHb concentrations respectively and +/-4% for SO(2) with an accuracy in the latter in the range -6%-+7%.

Evaluation of on-board kV cone beam CT (CBCT)-based dose calculation*

Abstract: On-board CBCT images are used to generate patient geometric models to assist patient setup. The image data can also, potentially, be used for dose reconstruction in combination with the fluence maps from treatment plan. Here we evaluate the achievable accuracy in using a kV CBCT for dose calculation. Relative electron density as a function of HU was obtained for both planning CT (pCT) and CBCT using a Catphan-600 calibration phantom. The CBCT calibration stability was monitored weekly for 8 consecutive weeks. A clinical treatment planning system was employed for pCT- and CBCT-based dose calculations and subsequent comparisons. Phantom and patient studies were carried out. In the former study, both Catphan-600 and pelvic phantoms were employed to evaluate the dosimetric performance of the full-fan and half-fan scanning modes. To evaluate the dosimetric influence of motion artefacts commonly seen in CBCT images, the Catphan-600 phantom was scanned with and without cyclic motion using the pCT and CBCT scanners. The doses computed based on the four sets of CT images (pCT and CBCT with/without motion) were compared quantitatively. The patient studies included a lung case and three prostate cases. The lung case was employed to further assess the adverse effect of intra-scan organ motion. Unlike the phantom study, the pCT of a patient is generally acquired at the time of simulation and the anatomy may be different from that of CBCT acquired at the time of treatment delivery because of organ deformation. To tackle the problem, we introduced a set of modified CBCT images (mCBCT) for each patient, which possesses the geometric information of the CBCT but the electronic density distribution mapped from the pCT with the help of a BSpline deformable image registration software. In the patient study, the dose computed with the mCBCT was used as a surrogate of the 'ground truth'. We found that the CBCT electron density calibration curve differs moderately from that of pCT. No significant fluctuation was observed in the calibration over the period of 8 weeks. For the static phantom, the doses computed based on pCT and CBCT agreed to within 1%. A notable difference in CBCT- and pCT-based dose distributions was found for the motion phantom due to the motion artefacts which appeared in the CBCT images (the maximum discrepancy was found to be approximately 3.0% in the high dose region). The motion artefacts-induced dosimetric inaccuracy was also observed in the lung patient study. For the prostate cases, the mCBCT- and CBCT-based dose calculations yielded very close results (<2%). Coupled with the phantom data, it is concluded that the CBCT can be employed directly for dose calculation for a disease site such as the prostate, where there is little motion artefact. In the prostate case study, we also noted a large discrepancy between the original treatment plan and the CBCT (or mCBCT)-based calculation, suggesting the importance of inter-fractional organ movement and the need for adaptive therapy to compensate for the anatomical changes in the future.

Acoustical properties of selected tissue phantom materials for ultrasound imaging.

Abstract: This note summarizes the characterization of the acoustic properties of four materials intended for the development of tissue, and especially breast tissue, phantoms for the use in photoacoustic and ultrasound imaging. The materials are agar, silicone, polyvinyl alcohol gel (PVA) and polyacrylamide gel (PAA). The acoustical properties, i.e., the speed of sound, impedance and acoustic attenuation, are determined by transmission measurements of sound waves at room temperature under controlled conditions. Although the materials are tested for application such as photoacoustic phantoms, we focus here on the acoustic properties, while the optical properties will be discussed elsewhere. To obtain the acoustic attenuation in a frequency range from 4 MHz to 14 MHz, two ultrasound sources of 5 MHz and 10 MHz core frequencies are used. For preparation, each sample is cast into blocks of three different thicknesses. Agar, PVA and PAA show similar acoustic properties as water. Within silicone polymer, a significantly lower speed of sound and higher acoustical attenuation than in water and human tissue were found. All materials can be cast into arbitrary shapes and are suitable for tissue-mimicking phantoms. Due to its lower speed of sound, silicone is generally less suitable than the other presented materials.

The ‘wet mind’: water and functional neuroimaging

Abstract: Functional neuroimaging has emerged as an important approach to study the brain and the mind. Surprisingly, although they are based on radically different physical approaches both positron emission tomography (PET) and magnetic resonance imaging (MRI) make brain activation imaging possible through measurements involving water molecules. So far, PET and MRI functional imaging have relied on the principle that neuronal activation and blood flow are coupled through metabolism. However, a new paradigm has emerged to look at brain activity through the observation with MRI of the molecular diffusion of water. In contrast with the former approaches diffusion MRI has the potential to reveal changes in the intrinsic water physical properties during brain activation, which could be more intimately linked to the neuronal activation mechanisms and lead to an improved spatial and temporal resolution. However, this link has yet to be fully confirmed and understood. To shed light on the possible relationship between water and brain activation, this introductory paper reviews the most recent data on the physical properties of water and on the status of water in biological tissues, and evaluates their relevance to brain diffusion MRI. The biophysical mechanisms of brain activation are then reassessed to reveal their intimacy with the physical properties of water, which may come to be regarded as the 'molecule of the mind'.

List-mode-based reconstruction for respiratory motion correction in PET using non-rigid body transformations

Abstract: Respiratory motion in emission tomography leads to reduced image quality. Developed correction methodology has been concentrating on the use of respiratory synchronized acquisitions leading to gated frames. Such frames, however, are of low signal-to-noise ratio as a result of containing reduced statistics. In this work, we describe the implementation of an elastic transformation within a list-mode-based reconstruction for the correction of respiratory motion over the thorax, allowing the use of all data available throughout a respiratory motion average acquisition. The developed algorithm was evaluated using datasets of the NCAT phantom generated at different points throughout the respiratory cycle. List-mode-data-based PET-simulated frames were subsequently produced by combining the NCAT datasets with Monte Carlo simulation. A non-rigid registration algorithm based on B-spline basis functions was employed to derive transformation parameters accounting for the respiratory motion using the NCAT dynamic CT images. The displacement matrices derived were subsequently applied during the image reconstruction of the original emission list mode data. Two different implementations for the incorporation of the elastic transformations within the one-pass list mode EM (OPL-EM) algorithm were developed and evaluated. The corrected images were compared with those produced using an affine transformation of list mode data prior to reconstruction, as well as with uncorrected respiratory motion average images. Results demonstrate that although both correction techniques considered lead to significant improvements in accounting for respiratory motion artefacts in the lung fields, the elastic-transformation-based correction leads to a more uniform improvement across the lungs for different lesion sizes and locations.

A simulation study on the resolution and sensitivity of magnetic particle imaging

Abstract: This paper presents the first detailed simulation approach to evaluate the proposed imaging method called 'magnetic particle imaging' with respect to resolution and sensitivity. The simulated scanner is large enough to accept human bodies. Together with the choice of field strength and noise the setup is representative for clinical applications. Good resolution, fast image acquisition and high sensitivity are demonstrated for various tracer concentrations, acquisition times, tracer properties and fields of view. Scaling laws for the simple prediction of image quality under the variation of these parameters are derived.

Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision open-ended coaxial probe

Abstract: Hepatic malignancies have historically been treated with surgical resection. Due to the shortcomings of this technique, there is interest in other, less invasive, treatment modalities, such as microwave hepatic ablation. Crucial to the development of this technique is the accurate knowledge of the dielectric properties of human liver tissue at microwave frequencies. To this end, we characterized the dielectric properties of in vivo and ex vivo normal, malignant and cirrhotic human liver tissues from 0.5 to 20 GHz. Analysis of our data at 915 MHz and 2.45 GHz indicates that the dielectric properties of ex vivo malignant liver tissue are 19 to 30% higher than normal tissue. The differences in the dielectric properties of in vivo malignant and normal liver tissue are not statistically significant (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 16% higher than normal). Also, the dielectric properties of in vivo normal liver tissue at 915 MHz and 2.45 GHz are 16 to 43% higher than ex vivo. No statistically significant differences were found between the dielectric properties of in vivo and ex vivo malignant tissue (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 28% higher than normal). We report the one-pole Cole-Cole parameters for ex vivo normal, malignant and cirrhotic liver tissue in this frequency range. We observe that wideband dielectric properties of in vivo liver tissue are different from the wideband dielectric properties of ex vivo liver tissue, and that the in vivo data cannot be represented in terms of a Cole-Cole model. Further work is needed to uncover the mechanisms responsible for the observed wideband trends in the in vivo liver data.

Real-time 3D computed tomographic reconstruction using commodity graphics hardware.

Abstract: The recent emergence of various types of flat-panel x-ray detectors and C-arm gantries now enables the construction of novel imaging platforms for a wide variety of clinical applications. Many of these applications require interactive 3D image generation, which cannot be satisfied with inexpensive PC-based solutions using the CPU. We present a solution based on commodity graphics hardware (GPUs) to provide these capabilities. While GPUs have been employed for CT reconstruction before, our approach provides significant speedups by exploiting the various built-in hardwired graphics pipeline components for the most expensive CT reconstruction task, backprojection. We show that the timings so achieved are superior to those obtained when using the GPU merely as a multi-processor, without a drop in reconstruction quality. In addition, we also show how the data flow across the graphics pipeline can be optimized, by balancing the load among the pipeline components. The result is a novel streaming CT framework that conceptualizes the reconstruction process as a steady flow of data across a computing pipeline, updating the reconstruction result immediately after the projections have been acquired. Using a single PC equipped with a single high-end commodity graphics board (the Nvidia 8800 GTX), our system is able to process clinically-sized projection data at speeds meeting and exceeding the typical flat-panel detector data production rates, enabling throughput rates of 40-50 projections s(-1) for the reconstruction of 512(3) volumes.

Improved k t BLAST and k t SENSE using FOCUSS

Abstract: The dynamic MR imaging of time-varying objects, such as beating hearts or brain hemodynamics, requires a significant reduction of the data acquisition time without sacrificing spatial resolution. The classical approaches for this goal include parallel imaging, temporal filtering and their combinations. Recently, model-based reconstruction methods called k-t BLAST and k-t SENSE have been proposed which largely overcome the drawbacks of the conventional dynamic imaging methods without a priori knowledge of the spectral support. Another recent approach called k-t SPARSE also does not require exact knowledge of the spectral support. However, unlike k-t BLAST/SENSE, k-t SPARSE employs the so-called compressed sensing (CS) theory rather than using training. The main contribution of this paper is a new theory and algorithm that unifies the above mentioned approaches while overcoming their drawbacks. Specifically, we show that the celebrated k-t BLAST/SENSE are the special cases of our algorithm, which is asymptotically optimal from the CS theory perspective. Experimental results show that the new algorithm can successfully reconstruct a high resolution cardiac sequence and functional MRI data even from severely limited k-t samples, without incurring aliasing artifacts often observed in conventional methods.

On the dosimetric behaviour of photon dose calculation algorithms in the presence of simple geometric heterogeneities: comparison with Monte Carlo calculations

Abstract: A comparative study was performed to reveal differences and relative figures of merit of seven different calculation algorithms for photon beams when applied to inhomogeneous media. The following algorithms were investigated: Varian Eclipse: the anisotropic analytical algorithm, and the pencil beam with modified Batho correction; Nucletron Helax-TMS: the collapsed cone and the pencil beam with equivalent path length correction; CMS XiO: the multigrid superposition and the fast Fourier transform convolution; Philips Pinnacle: the collapsed cone. Monte Carlo simulations (MC) performed with the EGSnrc codes BEAMnrc and DOSxyznrc from NRCC in Ottawa were used as a benchmark. The study was carried out in simple geometrical water phantoms (rho = 1.00 g cm(-3)) with inserts of different densities simulating light lung tissue (rho = 0.035 g cm(-3)), normal lung (rho = 0.20 g cm(-3)) and cortical bone tissue (rho = 1.80 g cm(-3)). Experiments were performed for low- and high-energy photon beams (6 and 15 MV) and for square (13 x 13 cm2) and elongated rectangular (2.8 x 13 cm2) fields. Analysis was carried out on the basis of depth dose curves and transverse profiles at several depths. Assuming the MC data as reference, gamma index analysis was carried out distinguishing between regions inside the non-water inserts or inside the uniform water. For this study, a distance to agreement was set to 3 mm while the dose difference varied from 2% to 10%. In general all algorithms based on pencil-beam convolutions showed a systematic deficiency in managing the presence of heterogeneous media. In contrast, complicated patterns were observed for the advanced algorithms with significant discrepancies observed between algorithms in the lighter materials (rho = 0.035 g cm(-3)), enhanced for the most energetic beam. For denser, and more clinical, densities a better agreement among the sophisticated algorithms with respect to MC was observed.

Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

Abstract: Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches—although conceptually different—yield very similar results on a qualitative level.

High-resolution brain tumor visualization using three-dimensional x-ray phase contrast tomography

Abstract: We report on significant advances and new results concerning a recently developed method for grating-based hard x-ray phase tomography. We demonstrate how the soft tissue sensitivity of the technique is increased and show in vitro tomographic images of a tumor bearing rat brain sample, without use of contrast agents. In particular, we observe that the brain tumor and the white and gray brain matter structure in a rat's cerebellum are clearly resolved. The results are potentially interesting from a clinical point of view, since a similar approach using three transmission gratings can be implemented with more readily available x-ray sources, such as standard x-ray tubes. Moreover, the results open the way to in vivo experiments in the near future.

GPU-based streaming architectures for fast cone-beam CT image reconstruction and demons deformable registration.

Abstract: This paper shows how to significantly accelerate cone-beam CT reconstruction and 3D deformable image registration using the stream-processing model. We describe data-parallel designs for the Feldkamp, Davis and Kress (FDK) reconstruction algorithm, and the demons deformable registration algorithm, suitable for use on a commodity graphics processing unit. The streaming versions of these algorithms are implemented using the Brook programming environment and executed on an NVidia 8800 GPU. Performance results using CT data of a preserved swine lung indicate that the GPU-based implementations of the FDK and demons algorithms achieve a substantial speedup—up to 80 times for FDK and 70 times for demons when compared to an optimized reference implementation on a 2.8 GHz Intel processor. In addition, the accuracy of the GPU-based implementations was found to be excellent. Compared with CPU-based implementations, the RMS differences were less than 0.1 Hounsfield unit for reconstruction and less than 0.1 mm for deformable registration.

Application of the noise power spectrum in modern diagnostic MDCT: part I. Measurement of noise power spectra and noise equivalent quanta.

Abstract: Dose reduction efforts in diagnostic CT have brought the tradeoff of dose versus image quality to the forefront. The need for meaningful characterization of image noise beyond that offered by pixel standard deviation is becoming increasingly important. This work aims to study the implementation of the noise power spectrum (NPS) and noise equivalent quanta (NEQ) on modern, multislice diagnostic CT scanners. The details of NPS and NEQ measurement are outlined and special attention is paid to issues unique to multislice CT. Aliasing, filter design and effects of acquisition geometry are investigated. While it was found that both metrics can be implemented in modern CT, it was discovered that NEQ cannot be aptly applied with certain non-traditional reconstruction filters or in helical mode. NPS and NEQ under a variety of conditions are examined. Extensions of NPS and NEQ to uses in protocol standardization are also discussed.

A boundary-representation method for designing whole-body radiation dosimetry models: pregnant females at the ends of three gestational periods--RPI-P3, -P6 and -P9.

Abstract: Fetuses are extremely radiosensitive and the protection of pregnant females against ionizing radiation is of particular interest in many health and medical physics applications. Existing models of pregnant females relied on simplified anatomical shapes or partial-body images of low resolutions. This paper reviews two general types of solid geometry modeling: constructive solid geometry (CSG) and boundary representation (BREP). It presents in detail a project to adopt the BREP modeling approach to systematically design whole-body radiation dosimetry models: a pregnant female and her fetus at the ends of three gestational periods of 3, 6 and 9 months. Based on previously published CT images of a 7-month pregnant female, the VIP-Man model and mesh organ models, this new set of pregnant female models was constructed using 3D surface modeling technologies instead of voxels. The organ masses were adjusted to agree with the reference data provided by the International Commission on Radiological Protection (ICRP) and previously published papers within 0.5%. The models were then voxelized for the purpose of performing dose calculations in identically implemented EGS4 and MCNPX Monte Carlo codes. The agreements of the fetal doses obtained from these two codes for this set of models were found to be within 2% for the majority of the external photon irradiation geometries of AP, PA, LAT, ROT and ISO at various energies. It is concluded that the so-called RPI-P3, RPI-P6 and RPI-P9 models have been reliably defined for Monte Carlo calculations. The paper also

Precautions and strategies in using a commercial flatbed scanner for radiochromic film dosimetry.

Abstract: The purpose of this study was to investigate the value of a commercially available flatbed scanner for film dosimetry with radiochromic film for external radiotherapy. The EPSON Pro 1680 Expression scanner was examined as a densitometer for two-dimensional film dosimetry with Gafchromic EBT film. An accurate and efficient scanning procedure was established. Possible drift and warm-up effects of the scanner were studied and the direct physical influence of the scanner light on the radiochromic film was assessed. Next, we investigated the scan field uniformity. Also, we examined if the accuracy of radiochromic film was improved by subtracting the optical density of the unirradiated blank film from the optical density of the irradiated film. To assess the accuracy of Gafchromic EBT film when the EPSON scanner was used as a densitometer, the depth dose of a 2 × 15 cm2 field and the in-plane and cross-plane profiles of a 15 × 15 cm2 field were measured and compared with diamond detector measurements. When taking consecutive scans, we found that the optical density taken from the first scan was about 1% higher than the optical density taken from subsequent scans. We attribute this to the warming up of the lamp of the scanner. Longer-term drift of the scanner was found to be absent. We found that the use of a correction matrix was necessary to correct for the non-uniform scanner response over the scan field. Subtracting the optical density of the unirradiated blank film from the irradiated film improves the precision of the Gafchromic EBT film. Depth dose and profile measurements with Gafchromic EBT film and the diamond detector are in agreement within 2.5%. The EPSON Pro 1680 Expression scanner is an excellent tool for accurate two-dimensional film dosimetry with Gafchromic EBT film provided that some precautions and corrections are taken into account.

Dosimetric characterization of GafChromic EBT film and its implication on film dosimetry quality assurance

Abstract: The suitability of radiochromic EBT film was studied for high-precision clinical quality assurance (QA) by identifying the dose response for a wide range of irradiation parameters typically modified in highly-conformal treatment techniques. In addition, uncertainties associated with varying irradiation conditions were determined. EBT can be used for dose assessment of absorbed dose levels as well as relative dosimetry when compared to absolute absorbed dose calibrated using ionization chamber results. For comparison, a silver halide film (Kodak EDR-2) representing the current standard in film dosimetry was included. As an initial step a measurement protocol yielding accurate and precise results was established for a flatbed transparency scanner (Epson Expression 1680 Pro) that was utilized as a film reading instrument. The light transmission measured by the scanner was found to depend on the position of the film on the scanner plate. For three film pieces irradiated with doses of 0 Gy, ~1 Gy and ~7 Gy, the pixel values measured in portrait or landscape mode differed by 4.7%, 6.2% and 10.0%, respectively. A study of 200 film pieces revealed an excellent sheet-to-sheet uniformity. On a long time scale, the optical development of irradiated EBT film consisted of a slow but steady increase of absorbance which was not observed to cease during 4 months. Sensitometric curves of EBT films obtained under reference conditions (SSD = 95 cm, FS = 5 × 5 cm2, d = 5 cm) for 6, 10 and 25 MV photon beams did not show any energy dependence. The average separation between all curves was only 0.7%. The variation of the depth d (range 2–25 cm) in the phantom did not affect the dose response of EBT film. Also the influence of the radiation field size (range 3 × 3–40 × 40 cm2) on the sensitometric curve was not significant. For EDR-2 films maximum differences between the calibration curves reached 7–8% for X6MV and X25MV. Radiochromic EBT film, in combination with a flatbed scanner, presents a versatile system for high-precision dosimetry in two dimensions, provided that the intrinsic behaviour of the film reading device is taken into account. EBT film itself presents substantial improvements on formerly available models of radiographic and a radiochromic film and its dosimetric characteristics allow us to measure absorbed dose levels in a large variety of situations with a single calibration curve.

Hybrid computational phantoms of the male and female newborn patient: NURBS-based whole-body models*

Abstract: Anthropomorphic computational phantoms are computer models of the human body for use in the evaluation of dose distributions resulting from either internal or external radiation sources. Currently, two classes of computational phantoms have been developed and widely utilized for organ dose assessment: (1) stylized phantoms and (2) voxel phantoms which describe the human anatomy via mathematical surface equations or 3D voxel matrices, respectively. Although stylized phantoms based on mathematical equations can be very flexible in regard to making changes in organ position and geometrical shape, they are limited in their ability to fully capture the anatomic complexities of human internal anatomy. In turn, voxel phantoms have been developed through image-based segmentation and correspondingly provide much better anatomical realism in comparison to simpler stylized phantoms. However, they themselves are limited in defining organs presented in low contrast within either magnetic resonance or computed tomography images-the two major sources in voxel phantom construction. By definition, voxel phantoms are typically constructed via segmentation of transaxial images, and thus while fine anatomic features are seen in this viewing plane, slice-to-slice discontinuities become apparent in viewing the anatomy of voxel phantoms in the sagittal or coronal planes. This study introduces the concept of a hybrid computational newborn phantom that takes full advantage of the best features of both its stylized and voxel counterparts: flexibility in phantom alterations and anatomic realism. Non-uniform rational B-spline (NURBS) surfaces, a mathematical modeling tool traditionally applied to graphical animation studies, was adopted to replace the limited mathematical surface equations of stylized phantoms. A previously developed whole-body voxel phantom of the newborn female was utilized as a realistic anatomical framework for hybrid phantom construction. The construction of a hybrid phantom is performed in three steps: polygonization of the voxel phantom, organ modeling via NURBS surfaces and phantom voxelization. Two 3D graphic tools, 3D-DOCTOR and Rhinoceros, were utilized to polygonize the newborn voxel phantom and generate NURBS surfaces, while an in-house MATLAB code was used to voxelize the resulting NURBS model into a final computational phantom ready for use in Monte Carlo radiation transport calculations. A total of 126 anatomical organ and tissue models, including 38 skeletal sites and 31 cartilage sites, were described within the hybrid phantom using either NURBS or polygon surfaces. A male hybrid newborn phantom was constructed following the development of the female phantom through the replacement of female-specific organs with male-specific organs. The outer body contour and internal anatomy of the NURBS-based phantoms were adjusted to match anthropometric and reference newborn data reported by the International Commission on Radiological Protection in their Publication 89. The voxelization process was designed to accurately convert NURBS models to a voxel phantom with minimum volumetric change. A sensitivity study was additionally performed to better understand how the meshing tolerance and voxel resolution would affect volumetric changes between the hybrid-NURBS and hybrid-voxel phantoms. The male and female hybrid-NURBS phantoms were constructed in a manner so that all internal organs approached their ICRP reference masses to within 1%, with the exception of the skin (-6.5% relative error) and brain (-15.4% relative error). Both hybrid-voxel phantoms were constructed with an isotropic voxel resolution of 0.663 mm--equivalent to the ICRP 89 reference thickness of the newborn skin (dermis and epidermis). Hybrid-NURBS phantoms used to create their voxel counterpart retain the non-uniform scalability of stylized phantoms, while maintaining the anatomic realism of segmented voxel phantoms with respect to organ shape, depth and inter-organ positioning.

Depth of interaction decoding of a continuous crystal detector module.

Abstract: We present a clustering method to extract the depth of interaction (DOI) information from an 8 mm thick crystal version of our continuous miniature crystal element (cMiCE) small animal PET detector. This clustering method, based on the maximum-likelihood (ML) method, can effectively build look-up tables (LUT) for different DOI regions. Combined with our statistics-based positioning (SBP) method, which uses a LUT searching algorithm based on the ML method and two-dimensional mean–variance LUTs of light responses from each photomultiplier channel with respect to different gamma ray interaction positions, the position of interaction and DOI can be estimated simultaneously. Data simulated using DETECT2000 were used to help validate our approach. An experiment using our cMiCE detector was designed to evaluate the performance. Two and four DOI region clustering were applied to the simulated data. Two DOI regions were used for the experimental data. The misclassification rate for simulated data is about 3.5% for two DOI regions and 10.2% for four DOI regions. For the experimental data, the rate is estimated to be ~25%. By using multi-DOI LUTs, we also observed improvement of the detector spatial resolution, especially for the corner region of the crystal. These results show that our ML clustering method is a consistent and reliable way to characterize DOI in a continuous crystal detector without requiring any modifications to the crystal or detector front end electronics. The ability to characterize the depth-dependent light response function from measured data is a major step forward in developing practical detectors with DOI positioning capability.

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer.

Abstract: With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was approximately 4.0 cGy, which was approximately 40% higher than the Rt Lat dose of approximately 2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm x 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370 degrees scan rotation (10 degrees scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of approximately 10-11 cGy while the right hip received approximately 6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than approximately 12% to the table-drop setup.

Clinical CT-based calculations of dose and positron emitter distributions in proton therapy using the FLUKA Monte Carlo code

Abstract: Clinical investigations on post-irradiation PET/CT (positron emission tomography/computed tomography) imaging for in vivo verification of treatment delivery and, in particular, beam range in proton therapy are underway at Massachusetts General Hospital (MGH). Within this project, we have developed a Monte Carlo framework for CT-based calculation of dose and irradiation-induced positron emitter distributions. Initial proton beam information is provided by a separate Geant4 Monte Carlo simulation modelling the treatment head. Particle transport in the patient is performed in the CT voxel geometry using the FLUKA Monte Carlo code. The implementation uses a discrete number of different tissue types with composition and mean density deduced from the CT scan. Scaling factors are introduced to account for the continuous Hounsfield unit dependence of the mass density and of the relative stopping power ratio to water used by the treatment planning system (XiO (Computerized Medical Systems Inc.)). Resulting Monte Carlo dose distributions are generally found in good correspondence with calculations of the treatment planning program, except a few cases (e.g. in the presence of air/tissue interfaces). Whereas dose is computed using standard FLUKA utilities, positron emitter distributions are calculated by internally combining proton fluence with experimental and evaluated cross-sections yielding 11C, 15O, 14O, 13N, 38K and 30P. Simulated positron emitter distributions yield PET images in good agreement with measurements. In this paper, we describe in detail the specific implementation of the FLUKA calculation framework, which may be easily adapted to handle arbitrary phase spaces of proton beams delivered by other facilities or include more reaction channels based on additional cross-section data. Further, we demonstrate the effects of different acquisition time regimes (e.g., PET imaging during or after irradiation) on the intensity and spatial distribution of the irradiation-induced beta+-activity signal for the cases of head and neck and para-spinal tumour sites.

Automatic estimation of the noise variance from the histogram of a magnetic resonance image

Abstract: Estimation of the noise variance of a magnetic resonance (MR) image is important for various post-processing tasks. In the literature, various methods for noise variance estimation from MR images are available, most of which however require user interaction and/or multiple (perfectly aligned) images. In this paper, we focus on automatic histogram-based noise variance estimation techniques. Previously described methods are reviewed and a new method based on the maximum likelihood (ML) principle is presented. Using Monte Carlo simulation experiments as well as experimental MR data sets, the noise variance estimation methods are compared in terms of the root mean squared error (RMSE). The results show that the newly proposed method is superior in terms of the RMSE.