Novel MRI and CT compatible stereotactic brain biopsy system in dogs using patient-specific facemasks.

OBJECTIVE: The objective of this pilot study was to describe the application and first preliminary data of a novel MRI and CT compatible patient-specific facemask for stereotactic brain biopsy of intracranial lesions in dogs. METHODS: Five client-owned dogs presenting for neurological deficits consistent with forebrain disease were included in the study. All dogs had MRI findings consistent with an intracranial lesion. Using images obtained from either MRI or CT, a virtual three-dimensional model of each dog's face was generated. The contact surface of each dog's face was selected for facemask design and a target point for biopsy was chosen using specialised software and toolkits. A patient-specific facemask with an attached biopsy port with premeasured and preselected trajectory was then fabricated by a 3D printer. The facemasks were sterilised and used intraoperatively to obtain biopsy samples. Biopsy samples were submitted for both cytological and histopathological evaluation. RESULTS: The diagnostic yield based on specific histological diagnosis was 80%. The one case in which a histological diagnosis could not be confirmed had a cytological interpretation consistent with meningioma. No major complications were observed during or immediately after brain biopsy and all dogs were discharged from the hospital within 72 hours postprocedure. CLINICAL SIGNIFICANCE: In conclusion, patient-specific facemasks appear to be a safe and effective method of brain biopsy in dogs, with minimal complications observed.

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs.

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.

An image-based skeletal model for the ICRP reference adult male-specific absorbed fractions for neutron-generated recoil protons.

Recoiling hydrogen nuclei are a principle mechanism for energy deposition from incident neutrons. For neutrons incident on the human skeleton, the small sizes of two contrasting media (trabecular bone and marrow) present unique problems due to a lack of charged-particle (protons) equilibrium. Specific absorbed fractions have been computed for protons originating in the human skeletal tissues for use in computing neutron dose response functions. The proton specific absorbed fractions were computed using a pathlength-based range-energy calculation in trabecular skeletal samples of a 40 year old male cadaver.

Radiosensitivity and capacity for radiation-induced sublethal damage repair of canine transitional cell carcinoma (TCC) cell lines.

Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/ß ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/ß ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC.

Methods for the inclusion of shallow marrow and adipose tissue in pathlength-based skeletal dosimetry.

Distributions of linear pathlength measurements have been utilized in skeletal dosimetry of internally emitted short-range particles for over 30 years. This work reviews the methods for coupling these distributions to range-energy data. A revised methodology is presented for handling the insertion of the additional dosimetric target region (shallow marrow) and medium (adipose tissue) into the dosimetry algorithm. The methodology is shown to reduce the volume fraction of shallow marrow in the trabecular skeleton over existing methodologies. Finally, theoretical low and high-energy checkpoints are derived for use in checking the absorbed fraction and specific absorbed fraction results for a variety of source and target combinations.

Skeletal absorbed fractions for electrons in the adult male: considerations of a revised 50-microm definition of the bone endosteum.

In 1995, the International Commission on Radiological Protection (ICRP) issued ICRP Publication 70 which provided an extensive update to the physiological and anatomical reference data for the skeleton of adults and children originally issued in ICRP Publication 23. Although ICRP Publication 70 has been a valuable document in the development of reference voxel computational phantoms, additional guidance is needed for dose assessment in the skeletal tissues beyond that given in ICRP Publication 30. In this study, a computed tomography (CT) and micro-CT-based model of the skeletal tissues is presented, which considers (1) a 50-microm depth in marrow for the osteoprogenitor cells, (2) electron escape from trabecular spongiosa to the surrounding cortical bone, (3) cortical bone to trabecular spongiosa cross-fire for electrons and (4) variations in specific absorbed fraction with changes in bone marrow cellularity for electrons. A representative data set is given for electron dosimetry in the craniofacial bones of the adult male.

Image segmentation of trabecular spongiosa by visual inspection of the gradient magnitude.

Recent advances in physical models of skeletal dosimetry utilize high-resolution 3-dimensional microscopic computed tomography images of trabecular spongiosa. These images are coupled to radiation transport codes to assess energy deposition within active bone marrow and trabecular endosteum. These transport codes rely primarily on the segmentation of the spongiosa images into bone and marrow voxels. Image thresholding has been the segmentation of choice for bone sample images because of its extreme simplicity. However, the ability of the segmentation to reproduce the physical boundary between bone and marrow depends on the selection of the threshold value. Statistical models, as well as visual inspection of the image, have been employed extensively to determine the correct threshold. Both techniques are affected by partial volume effect and can provide unexpected results if performed without care. In this study, we propose a new technique to threshold trabecular spongiosa images based on visual inspection of the image gradient magnitude. We first show that the gradient magnitude of the image reaches a maximum along a surface that remains almost independent of partial volume effect and that is a good representation of the physical boundary between bone and marrow. A computer program was then developed to allow a user to compare the position of the iso-surface produced by a threshold with the gradient magnitude. The threshold that produces the iso-surface that best coincides with the maximum gradient is chosen. The technique was finally tested with a set of images of a true bone sample with different resolutions, as well as with three images of a cube of Duocell aluminium foam of known mass and density. Both tests demonstrate the ability of the gradient magnitude technique to retrieve sample volumes or media volume fractions with 1% accuracy at 30 microm voxel size.

A hyperboliod representation of the bone-marrow interface within 3D NMR images of trabecular bone: applications to skeletal dosimetry.

Recent advances in physical models of skeletal dosimetry utilize high-resolution NMR microscopy images of trabecular bone. These images are coupled to radiation transport codes to assess energy deposition within active bone marrow irradiated by bone- or marrow-incorporated radionuclides. Recent studies have demonstrated that the rectangular shape of image voxels is responsible for cross-region (bone-to-marrow) absorbed fraction errors of up to 50% for very low-energy electrons (<50 keV). In this study, a new hyperboloid adaptation of the marching cube (MC) image-visualization algorithm is implemented within 3D digital images of trabecular bone to better define the bone-marrow interface, and thus reduce voxel effects in the assessment of cross-region absorbed fractions. To test the method, a mathematical sample of trabecular bone was constructed, composed of a random distribution of spherical marrow cavities, and subsequently coupled to the EGSnrc radiation code to generate reference values for the energy deposition in marrow or bone. Next, digital images of the bone model were constructed over a range of simulated image resolutions, and coupled to EGSnrc using the hyperboloid MC (HMC) algorithm. For the radionuclides 33P, 117mSn, 131I and 153Sm, values of S(marrow<--bone) estimated using voxel models of trabecular bone were shown to have relative errors of 10%, 9%, <1% and <1% at a voxel size of 150 microm. At a voxel size of 60 microm, these errors were 6%, 5%, <1% and <1%, respectively. When the HMC model was applied during particle transport, the relative errors on S(marrow<--bone) for these same radionuclides were reduced to 7%, 6%, <1% and <1% at a voxel size of 150 microm, and to 2%, 2%, <1% and <1% at a voxel size of 60 microm. The technique was also applied to a real NMR image of human trabecular bone with a similar demonstration of reductions in dosimetry errors.

Marching cube algorithm: review and trilinear interpolation adaptation for image-based dosimetric models.

Current internal organ dose assessment methodologies utilize three-dimensional (3D) medical images of the body to model organ shapes and tissue interfaces. These models are coupled to computer programs that measure radionuclide energy deposition or chord-length distributions directly within these images. Previous studies have shown that the rectangular shape of image voxels generates voxel effects that alter the outcome of these calculations. To minimize voxel effects, the present study proposes to use the Marching Cube (MC) algorithm to generate isosurfaces delineating tissue interfaces from the gray-level images. First, a review of the different techniques surrounding the MC algorithm is presented. Next, an adaptation of the algorithm is proposed in which a trilinear interpolation of the gray levels is used to generate a hyperboloid surface within the MCs. This new technique is shown to solve the classic ambiguity problem of the MC algorithm and also to reduce the data size inherent to the triangulated surface. It also provides a simple algorithm to accurately measure distances within the image. The technique is then tested with a mathematical model of trabecular bone. The trilinear interpolation method is shown to remove voxel effects and to produce reliable chord-length distributions across image regions. The technique is thus recommended for use with digital medical images needed for internal radiation transport simulations. The current study is performed for a single isosurface that separates two media within the same image, but it is proposed that the technique can be extended to multiple isosurfaces that delineate several organs or organ regions within 3D tomographic voxels of human anatomy.

Interactions with 3D isotropic and homogeneous radiation fields: a Monte Carlo simulation algorithm.

Monte Carlo techniques have become important tools for many biomedical applications. Many of these involve simulations of radiation fields that rely on the isotropy and homogeneity of the radiation source. The current study proposes a general algorithm to simulate such a radiation field around a fixed object. The idea is to surround the object with a sphere and to limit the source of radiation to the surface of that sphere. To insure the isotropy of the radiation source, each point on the sphere surface as seen from the object defines a direction at which a unidirectional field of particles is created. The combination of all unidirectional fields approaching from all points on the source sphere creates the effect of an isotropic and homogeneous radiation source. The algorithm is first presented without mathematical detail. Next, the expressions for the position and direction of the particles that compose the field are derived using analytical geometry. The radius of the source sphere is the only parameter needed for this algorithm. The randomness of each particle is simulated by the choice of four random numbers. Two algorithms using these analytical results are proposed, and an example of a C program is given for each. Both algorithms can be easily adapted to any situation that involves the Monte Carlo simulation of radiation interactions of a fixed object immersed within an isotropic and homogeneous radiation field.

Considerations of anthropometric, tissue volume, and tissue mass scaling for improved patient specificity of skeletal S values.

It is generally acknowledged that reference man (70 kg in mass and 170 cm in height) does not adequately represent the stature and physical dimensions of many patients undergoing radionuclide therapy, and thus scaling of radionuclide S values is required for patient specificity. For electron and beta sources uniformly distributed within internal organs, the mean dose from self-irradiation is noted to scale inversely with organ mass, provided no escape of electron energy occurs at the organ boundaries. In the skeleton, this same scaling approach is further assumed to be correct for marrow dosimetry; nevertheless, difficulties in quantitative assessments of marrow mass in specific skeletal regions of the patient make this approach difficult to implement clinically. Instead, scaling of marrow dose is achieved using various anthropometric parameters that presumably scale in the same proportion. In this study, recently developed three-dimensional macrostructural transport models of the femoral head and humeral epiphysis in three individuals (51-year male, 82-year female, and 86-year female) are used to test the abilities of different anthropometric parameters (total body mass, body surface area, etc.) to properly scale radionuclide S values from reference man models. The radionuclides considered are 33P, 177Lu, 153Sm, 186Re, 89Sr, 166Ho, 32P, 188Re, and 90Y localized in either the active marrow or endosteal tissues of the bone trabeculae. S value scaling is additionally conducted in which the 51-year male subject is assigned as the reference individual; scaling parameters are then expanded to include tissue volumes and masses for both active marrow and skeletal spongiosa. The study concludes that, while no single anthropometric parameter emerges as a consistent scaler of reference man S values, lean body mass is indicated as an optimal scaler when the reference S values are based on 3D transport techniques. Furthermore, very exact patient-specific scaling of radionuclide S values can be achieved if measurements of spongiosa volume and marrow volume fraction (high-resolution CT with image segmentation) are known in both the patient and the reference individual at skeletal sites for which dose estimates are sought. However, the study indicates that measurements of the spongiosa volume alone may be sufficient for reasonable patient-specific scaling of S values for the majority of radionuclides of interest in internal-emitter therapy.

Voxel effects within digital images of trabecular bone and their consequences on chord-length distribution measurements.

Chord-length distributions through the trabecular regions of the skeleton have been investigated since the early 1960s. These distributions have become important features for bone marrow dosimetry; as such, current models rely on the accuracy of their measurements. Recent techniques utilize nuclear magnetic resonance (NMR) microscopy to acquire 3D images of trabecular bone that are then used to measure 3D chord-length distributions by Monte Carlo methods. Previous studies have shown that two voxel effects largely affect the acquisition of these distributions within digital images. One is particularly pertinent as it dramatically changes the shape of the distribution and reduces its mean. An attempt was made to reduce this undesirable effect and good results were obtained for a single-sphere model using minimum acceptable chord (MAC) methods (Jokisch et al 2001 Med. Phys. 28 1493-504). The goal of the present work is to extend the study of these methods to more general models in order to better quantify their consequences. First, a mathematical model of a trabecular bone sample was used to test the usefulness of the MAC methods. The results showed that these methods were not efficient for this simulated bone model. These methods were further tested on a single voxelized sphere over a large range of voxel sizes. The results showed that the MAC methods are voxel-size dependent and overestimate the mean chord length for typical resolutions used with NMR microscopy. The study further suggests that bone and marrow chord-length distributions currently utilized in skeletal dosimetry models are most likely affected by voxel effects that yield values of mean chord length lower than their true values.

Surface area overestimation within three-dimensional digital images and its consequence for skeletal dosimetry.

The most recent methods for trabecular bone dosimetry are based on Monte Carlo transport simulations within three-dimensional (3D) images of real human bone samples. Nuclear magnetic resonance and micro-computed tomography have been commonly used as imaging tools for studying trabecular microstructure. In order to evaluate the accuracy of these techniques for radiation dosimetry, a previous study was conducted that showed an overestimate in the absorbed fraction of energy for low-energy electrons emitted within the marrow space and irradiating the bone trabeculae. This problem was found to be related to an overestimate of the surface area of the true bone-marrow interface within the 3D digital images, and was identified as the surface-area effect. The goal of the present study is to better understand how this surface-area effect occurs in the case of single spheres representing individual marrow cavities within trabecular bone. First, a theoretical study was conducted which showed that voxelization of the spherical marrow cavity results in a 50% overestimation of the spherical surface area. Moreover, this overestimation cannot be reduced through a reduction in the voxel size (e.g., improved image resolution). Second, a series of single-sphere marrow cavity models was created with electron sources simulated within the sphere (marrow source) and outside the sphere (bone trabeculae source). The series of single-sphere models was then voxelized to represent 3D digital images of varying resolution. Transport calculations were made for both marrow and bone electron sources within these simulated images. The study showed that for low-energy electrons (<100 keV), the 50% overestimate of the bone-marrow interface surface area can lead to a 50% overestimate of the cross-absorbed fraction. It is concluded that while improved resolution will not reduce the surface area effects found within 3D image-based transport models, a tenfold improvement in current image resolution would compensate the associated errors in cross-region absorbed fractions for low-energy electron sources. Alternatively, other methods of defining the bone-marrow interface, such as with a polygonal isosurface, would provide improvements in dosimetry without the need for drastic reductions in image voxel size.

Skeletal dosimetry via NMR microscopy: investigations of sample reproducibility and signal source.

Nuclear magnetic resonance microscopy has been used for several years as a means of quantifying the 3D microarchitecture of the cancellous regions of the skeleton. These studies were originally undertaken for the purpose of developing non-invasive techniques for the early detection of osteoporosis and other bone structural changes. Recently, nuclear magnetic resonance microscopy has also been used to acquire this same 3D data for the purpose of both (1) generating chord length data across bone trabeculae and marrow cavities and (2) generating 3D images for direct coupling to Monte Carlo radiation transport codes. In both cases, one is interested in the reproducibility of the dosimetric data obtained from nuclear magnetic resonance microscopy. In the first of two studies, a trabecular bone sample from the femoral head of a 51-y-old male cadaver was subjected to repeated image acquisition, image processing, image coupling, and radiation transport simulations. The resulting absorbed fractions at high electron energies (4 MeV) were shown to vary less than 4% among four different imaging sessions of the same sample. In a separate study, two femoral head samples were imaged under differing conditions of the NMR signal source. In the first case, the samples were imaged with intact marrow. These samples were then subjected to marrow digestion and immersed in Gd-doped water, which then filled the marrow cavities. Energy-dependent absorbed fraction profiles for both the marrow-intact and marrow-free samples showed essentially equivalent results. These studies thus provide encouragement that skeletal dosimetry models of improved patient specificity can be achieved via NMR microscopy in vivo.

Site-specific variability in trabecular bone dosimetry: considerations of energy loss to cortical bone.

With continual advances in radionuclide therapies, increasing emphasis is being placed on improving the patient specificity of dose estimates to marrow tissues. While much work has been focused on determining patient-specific assessments of radionuclide uptake in the skeleton, few studies have been initiated to explore the individual variability of absorbed fraction data for electron and beta-particle sources in various skeletal sites. The most recent values of radionuclide S values used in clinical medicine continue to utilize a formalism in which electrons are transported under a trabecular bone geometry of infinite extent. No provisions are thus made for the fraction of energy lost to the cortical bone cortex of the skeletal site and its surrounding tissues. In the present study, NMR microscopy was performed on trabecular bone samples taken from the femoral head and humeral proximal epiphysis of three subjects: a 51-year male, an 82-year female, and an 86-year female. Following image segmentation and coupling to EGS4, electrons were transported within macrostructural models of the various skeletal sites that explicitly include the spatial extent of the spongiosa, as well as the thickness of the surrounding cortical bone. These energy-dependent profiles of absorbed fractions to marrow tissues were then compared to transport simulations made within an infinite region of spongiosa. Ratios of mean absorbed fraction, as weighted by the beta energy spectra, under both transport methodologies were then assembled for the radionuclides 32P and 90Y. These ratios indicate that corrections to existing radionuclide S values for 32P can vary by as much as 5% for the male, 6% for the 82-year female, and 8% for the 86-year female. For the higher-energy beta spectrum of 90Y, these same corrections can reach 8%, 10%, and 11%, respectively.

Chord distributions across 3D digital images of a human thoracic vertebra.

Radiation dose estimates to the trabecular region of the skeleton are of primary importance due to recent advancements in nuclear medicine. Establishing methods for accurately calculating dose in these regions is difficult due to the complex microstructure of this anatomic site and the typical ranges of beta-particles in both bone and marrow tissues. At the present time, models of skeletal dosimetry used in clinical medicine rely upon measured distributions of straight-line path lengths (chord lengths) through bone and marrow regions. This work develops a new three-dimensional, digital method for acquiring these distributions within voxelized images. In addition, the study details the characteristics of measuring chord distributions within digital images and provides a methodology for avoiding undesirable pixel or voxel effects. The improved methodology has been applied to a digital image (acquired via NMR microscopy) of the trabecular region of a human thoracic vertebra. The resulting chord-length distributions across both bone trabeculae and bone marrow cavities were found to be in general agreement with those measured in other studies utilizing different methods. In addition, this study identified that bone and marrow space chord-length distributions are not statistically independent, a condition implicitly assumed within all current skeletal dosimetry models of electron transport. The study concludes that the use of NMR microscopy combined with the digital measurement techniques should be used to further expand the existing Reference Man database of trabecular chord distributions to permit the development of skeletal dosimetry models which are more age and gender specific.

Beta-particle dosimetry of the trabecular skeleton using Monte Carlo transport within 3D digital images.

Presently, skeletal dosimetry models utilized in clinical medicine simulate electron path lengths through skeletal regions based upon distributions of linear chords measured across bone trabeculae and marrow cavities. In this work, a human thoracic vertebra has been imaged via nuclear magnetic resonance (NMR) spectroscopy yielding a three-dimensional voxelized representation of this skeletal site. The image was then coupled to the radiation transport code EGS4 allowing for 3D tracing of electron paths within its true 3D structure. The macroscopic boundaries of the trabecular regions, as well as the cortex of cortical bone surrounding the bone site, were explicitly considered in the voxelized transport model. For the case of a thoracic vertebra, energy escape to the cortical bone became significant at source energies exceeding approximately 2 MeV. Chord-length distributions were acquired from the same NMR image, and subsequently used as input for a chord-based dosimetry model. Differences were observed in the absorbed fractions given by the chord-based model and the voxel transport model, suggesting that some of the input chord distributions for the chord-based models may not be accurate. Finally, this work shows that skeletal mass estimates can be made from the same NMR image in which particle transport is performed. This feature allows one to determine a skeletal S-value using absorbed fraction and mass data taken from the same anatomical tissue sample. The techniques developed in this work may be applied to a variety of skeletal sites, thus allowing for the development of skeletal dosimetry models at all skeletal sites for both males and females and as a function of subject age.

Voxel size effects in three-dimensional nuclear magnetic resonance microscopy performed for trabecular bone dosimetry.

An important problem in internal dosimetry is the assessment of energy deposition by beta particles within trabecular regions of the skeleton. Recent dosimetry methods for trabecular bone are based on Monte Carlo particle transport simulations within three-dimensional (3D) images of real human bone samples. Nuclear magnetic resonance (NMR) microscopy is a 3D imaging technique of choice due to the large signal differential between bone tissue and the water-filled marrow cavities. Image voxel sizes currently used in NMR microscopy are between 50 microm and 100 microm, but the images are time consuming to acquire and can only be performed at present for in vitro samples. It is therefore important to evaluate what resolution is best suitable in order to properly characterize the trabecular microstructure, to adequately predict the tissue dosimetry, and to minimize imaging time. In this work, a mathematical model of trabecular bone, composed of a distribution of spherical marrow cavities, was constructed. The mathematical model was subsequently voxelized with different voxel sizes (16 microm to 1,000 microm) to simulate 3D NMR images. For each image, voxels are assigned to either bone or marrow according to their enclosed marrow fraction. Next, the images are coupled to the EGS4 electron transport code and absorbed fractions to bone and marrow are calculated for a marrow source of monoenergetic electrons. Radionuclide S values are also determined for the voxelized images with results compared to data calculated for the pure mathematical sample. The comparison shows that for higher energy electrons (>400 keV), good convergence of the results is seen even within images of poor resolution. Above 400 keV, a voxel resolution as large as 300 microm results in dosimetry errors below 5%. For low-energy electrons and high-resolution images, the self-dose to marrow is also determined to within 5% accuracy. Nevertheless, increased voxelization of the image overestimates the surface area of the bone-marrow interface leading to errors in the cross-dose to bone as high as 25% for some low-energy beta emitters.

NMR microscopy of trabecular bone and its role in skeletal dosimetry.

One of the more intractable problems in internal dosimetry is the assessment of energy deposition by alpha and beta particles within trabecular, or cancellous, bone. In the past few years, new technologies have emerged that allow for the direct and nondestructive 3D imaging of trabecular bone with sufficient spatial resolution to characterize trabecular bone structure in a manner needed for radiation dosimetry models. High-field proton nuclear magnetic resonance (NMR) imaging is one such technology. NMR is an ideal modality for imaging trabecular bone due to the sharp contrast in proton density between the bone matrix and bone marrow regions. In this study, images of the trabecular regions within the bodies of a human thoracic vertebra have been obtained at a field strength of 14.1 T. These images were digitally processed to measure chord length distribution data through both the bone trabeculae and marrow cavities. These distributions, which were found to be qualitatively consistent with those measured by F. W. Spiers and colleagues at the University of Leeds using physical sectioning and automated light microscopy, yielded a mean trabecular thickness of 201 microm and a mean marrow cavity thickness of 998 microm. The NMR techniques developed here for vertebral imaging may be extended to other skeletal sites, allowing for improved site-specific skeletal dosimetry.