Biomedical subjects

A P Shah

Publications and source records attributed to A P Shah.

16 recordsLinked to original sources

PubMed2006

Severe airflow obstruction and eosinophilic lung disease after Stevens-Johnson syndrome.

Respiratory involvement is a frequent complication of Stevens-Johnson syndrome (SJS). However, there are very few convincing reports of persistent pulmonary sequelae, as demonstrated by spirometry, radiology and pathology. The current study presents a case of a 13-yr-old female with T-cell acute lymphocytic leukaemia who developed persistent, severe, obstructive lung disease following an episode of SJS. A lung biopsy demonstrated bronchiolar submucosal fibrosis consistent with constrictive bronchiolitis, as well as eosinophilic micro-abscesses, which, to the current authors' knowledge, has not been previously described. The present study illustrates specific histopathological features that highlight a possible association between Stevens-Johnson syndrome, constrictive bronchiolitis and eosinophilic micro-abscesses. The eosinophils may be associated with permanent mucosal damage, as seen in the present case, by releasing mediators that have a pro-fibrogenetic role. However, further investigation is warranted.

Adolescent↗

PubMed2003

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.

Algorithms↗

PubMed2002

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.

Bone Marrow↗

PubMed2002

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.

Bone and Bones↗

PubMed2002

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.

Aged↗

PubMed2002

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.

Biophysical Phenomena↗

PubMed2000

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.

Bone Marrow↗

PubMed1978