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Biomedical subjects

Richard A Robb

Publications and source records attributed to Richard A Robb.

At least 19 recordsLinked to original sources

Schwarz meets Schwann: design and fabrication of biomorphic and durataxic tissue engineering scaffolds.

Tissue engineering is a discipline at the leading edge of the field of computer assisted intervention. This multidisciplinary engineering science attempts to meet the reparative and regenerative needs of tissues and organs based on the notion of design and fabrication of scaffolds- porous, three-dimensional "trellis-like" biomimetic structures that, on implantation, provide a viable environment to recuperate and regenerate damaged cells. Existing scaffold fabrication strategies produce sub-optimal porous labyrinths with contra-naturam straight edges. The biomorphic geometry that mimics the secundam-naturam substrate would be one that is continuous through all space, partitioned into two not-necessarily-equal sub-spaces by a non-intersecting, two-sided surface. Minimal surface geometry is not only ideal to describe such a space but is also the preferentially assumed geometry in natural and pathological or manipulated cells. We present results on the premier attempt in computer-controlled fabrication, modulation, and mechanical characterization of tissue engineering scaffolds based on triply periodic minimal surfaces (TPMS). We also present novel strategies to realize coterminous seeding-feeding networks thereby guaranteeing blood/nutrient supply to the proliferating cells at close proximity. This initiative of linking Schwann's 1838 cell theory with Schwarz's 1865 discovery of TPMS is a significant step to fabricate the previously elusive optimal biomorphic tissue analogs.

Animals↗

Biomedical image visualization research using the Visible Human Datasets.

The practice of medicine and conduct of research in major segments of the biologic sciences have always relied on visualizations to study the relationship of anatomic structure to biologic function. Traditionally, these visualizations have either been direct, via vivisection and postmortem examination, or have required extensive mental reconstruction. The revolutionary capabilities of 3-D and 4-D medical imaging modalities, together with computer reconstruction and rendering of multidimensional medical and histological volume image data, obviate the need for physical dissection or abstract assembly. The availability of the Visible Human Datasets from the National Library of Medicine, coupled with the development of advanced computer algorithms to accurately and rapidly process, segment, register, measure, and display high resolution 3-D images, has provided a rich opportunity to help advance these important new imaging, visualization, and analysis methodologies from scientific theory to clinical practice.

Algorithms↗

Age- and sex-specific differences in the factor of risk for vertebral fracture: a population-based study using QCT.

UNLABELLED: We used QCT scans obtained in 687 men and women, 21-97 years of age, to estimate the factor of risk for vertebral fracture, Phi(vert), defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Phi(vert) increased significantly more in women than men. Age- and sex-specific differences in Phi(vert) closely resembled previously reported vertebral fracture incidence. INTRODUCTION: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility. MATERIALS AND METHODS: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Phi(vert)) in an age- and sex-stratified population-based sample of 700 women and men 21-97 years of age. We measured volumetric BMD (vBMD, mg/cm3) and cross-sectional area (CSA, cm2) of the midvertebral bodies of L1-L3 using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L3 vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Phi(vert), was computed as the ratio of spinal compressive force to vertebral strength for each activity. RESULTS: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p < 0.001), the decline was greater in women than men (-43% versus -31%, p = 0.008). Compressive forces on L3 were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8-fold higher than those experienced during upright standing. For all activities, Phi(vert) increased with age, but significantly more so in women than men (p < 0.001). For bending and lifting, Phi(vert-bending) exceeded 1.0 in 30% of women and 12% of men > or =50 years of age, values that are similar to the reported frequency of vertebral fracture. CONCLUSION: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT-based biomechanical approach for assessment of fracture risk.

Adult↗

Does reduced skeletal loading account for age-related bone loss?

UNLABELLED: A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21-97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging. INTRODUCTION: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail. MATERIALS AND METHODS: In a stratified random sample of Rochester, MN, women and men 21-97 years of age, indices of bone strength, flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT measurements at the femoral neck and lumbar spine and pQCT measurements at the ultradistal radius, whereas habitual skeletal loading was assessed using lean body mass, total skeletal muscle mass (TSM), body weight, and physical activity. Using regression analysis, we tested the hypothesis (H(o)) that bone strength per unit load did not vary with age. RESULTS AND CONCLUSIONS: In these cross-sectional data, the null hypothesis of no age-related change was rejected in 72% of the strength-to-load ratios tested. For example, the ratio of femoral neck EI to TSM increased by 0.19%/year in women (p = 0.008) and by 0.49%/year in men (p < 0.001). There was no close correspondence between changes in habitual load and changes in bone strength, nor any consistent pattern. Moreover, interindividual variation in the strength-to-load ratios was substantial. These data suggest that the notion of reduced skeletal loading as the primary basis for age-related bone loss is oversimplified.

Adult↗

Virtual-reality-assisted interventional procedures.

Observable objects in biology and medicine extend across a range of scale, from individual molecules and cells; through the varieties of tissue and interstitial interfaces; and to complete organs, organ systems, and body parts. These objects include functional attributes of these systems such as biophysical, biomechanical, and physiologic properties. Imaging in three dimensions of such objects and their functions is possible now with the advent of high-resolution tomographic scanners and imaging systems. Medical applications include accurate anatomy and function mapping, enhanced diagnosis, accurate treatment planning and rehearsal, and education and training. Biologic applications include study and analysis of structure-to-function relationships in individual cells and organelles. The potential for revolutionary innovation in the practice of medicine and in biologic investigations lies in direct, fully immersive, real-time multisensory fusion of real and virtual information data streams into online, real-time images available during actual clinical procedures or biologic experiments. Current high-performance computing, advanced image processing and high-fidelity rendering capabilities have facilitated major progress toward realization of these goals. With these advances in hand, there are several important applications of three-dimensional viewing that will have a substantial impact on the practice of medicine.

Computer Simulation↗

Tissue engineering templates using minimal surfaces.

The status quo of tissue engineering can be summarized as "a random walk through the design space". The existing scaffold designs based on computeraided design (CAD) and solid freeform fabrication (SFF) are anti-biomorphic and mechanically weak cubic partitions with sharp edges. We introduce minimal surface based unit cells to create biomorphic scaffolds with optimal stress/strain distribution and superior mechanical strength.

Computer Simulation↗

TRUS-fluoroscopy fusion for intraoperative prostate brachytherapy dosimetry.

A fluoroscopic to TRUS fusion based approach for intraoperative prostate brachytherapy dosimetry was developed. Seed images were identified from multiple fluoroscopic images and reconstructed to determine the three dimensional distribution of the implanted seeds. Seeds identified from the TRUS images were used as fiducials for the registration between fluoroscopic and TRUS images. Dose analysis was then performed based on the fused images. A phantom study was performed to test this approach and a 3 mm registration error was observed. Radiation isodose contours were generated and superimposed on the TRUS images.

Brachytherapy↗

Optimal segmentation of microcomputed tomographic images of porous tissue-engineering scaffolds.

The morphometric properties of the porous tissue-engineering scaffolds play a dominant role in the initial cell attachment and subsequent tissue regeneration. These properties can be derived nondestructively with the use of quantitative analysis of high-resolution microcomputed tomography (microCT) imaging of scaffolds. Accurate segmentation of these acquired images into solid and porous subspaces is critical to the integrity of morphometric analysis. The absence of a single image-processing technique to provide such accurate separability immune to all the intricacies of the acquired data makes this seemingly simple task significantly error prone. Consequently, an optimal segmentation has to be selected by ranking the segmentations produced by a multiplicity of methods. This article proposes a robust, easy-to-implement, unambiguous, signal-processing-based, ground-truth-free, segmentation rating metric that correlates with visual acuity. With the use of this metric it is possible, for the first time, to threshold the data with a wide range of techniques and select automatically the technique that best delineates the acquired image. The proposed solution has been extensively tested on microCT images of scaffolds fabricated with biodegradable poly (propylene fumarate) (PPF) with the use of a solvent casting particulate leaching process. The approaches proposed and the results obtained may have profound implications for accurate image-based characterization of tissue-engineering scaffolds.

Biocompatible Materials↗

Population-based analysis of the relationship of whole bone strength indices and fall-related loads to age- and sex-specific patterns of hip and wrist fractures.

UNLABELLED: In an age- and sex-stratified population sample (n = 700), we estimated fall-related loads and bone strength indices at the UDR and FN. These load/strength ratios more closely simulated patterns of wrist and hip fractures occurring in the same population than did measurement of vBMD. INTRODUCTION: Areal BMD measurements, although associated with fracture risk, incompletely explain patterns of fragility fractures. Moreover, population-based assessments relating applied loads and whole bone strength to fracture patterns have not been made. MATERIALS AND METHODS: Using QCT, we assessed volumetric BMD (vBMD), cross-sectional geometry, and axial (EA) and flexural (EI) rigidities (indices of bone's resistance to compressive and bending loads, respectively) at the ultradistal radius (UDR) and femoral neck (FN) and estimated the loads applied to the wrist and hip during a fall. We used fall load (FL)/bone strength ratios to estimate fracture risk. RESULTS: vBMD in young adults was similar between sexes. Decreases in vBMD over life were also similar (30% and 28%) at UDR but were somewhat greater (46% and 34%) at FN in women versus men, respectively. In young adults, FL/strength ratios at UDR were 32-51% lower (better) in men than in women and increased (worsened) over life less in men (+4% to +22%) than in women (+20% to +33%). In young adults, FL/strength ratios at FN were only marginally better in men than in women but worsened less over life in men (+22% to +36%) than in women (+40% to +62%). CONCLUSIONS: The 6:1 female preponderance and the virtual immunity of men for age-related increases in wrist fractures are largely explained by the more favorable FL/strength ratios at UDR in young adult men (because of larger bone size and more favorable geometry) versus women and to maintaining this advantage over life. The 2-fold lower incidence of hip fractures in men versus women is largely explained by age-related increases (worsening) of FL/bone strength ratios that are only one-half of the increases in women. The moderate increases in these ratios with aging are insufficient to explain the >4-fold increase in hip fracture incidence after age 75 in both sexes, suggesting contributions of other factors, especially the well-documented increased frequency of injurious falls among the elderly.

Absorptiometry, Photon↗

Spatiotemporal gait deviations in a virtual reality environment.

Previous research suggests that postural sway in standing increases in virtual reality (VR) environments. This study was conducted to examine whether gait instability is prevalent when people walk in a VR environment. Ten healthy adults participated in the study. Subjects walked on a treadmill in a VR environment and a non-VR environment at each of three walking speeds: 0.9, 1.1, and 1.3 m/s. In the VR environment, an endless corridor with colored vertical stripes comprising the walls was projected onto a hemispherical screen placed in front of the treadmill. The speed of the moving corridor image was matched to the speed of the treadmill to create the illusion that subjects were walking through the endless corridor. Spatiotemporal data during gait were collected with an instrumented treadmill housing two piezoelectric force platforms. Gait parameters reflective of gait instability (stride length, step width, variability in stride velocity, and variability in step width) were compared between the VR and non-VR environments. Subjects walked in the VR environment with reduced stride lengths (p = 0.001), increased step widths (p = 0.001), and with increased variability in stride velocity (p < 0.001) and step width (p = 0.002). The gait deviations suggest that walking in a VR environment may induce gait instability in healthy subjects.

Adult↗

Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in women.

CONTEXT: Although estrogen clearly plays a central role in regulating bone mass in women, studies in men have suggested that there may be a threshold bioavailable (bio) estradiol (E2) level below which aging men begin to lose bone and that the threshold for estrogen deficiency in cortical bone may be considerably lower than that in trabecular bone. There are no data testing this in women. OBJECTIVE: Our objective was to assess volumetric bone mineral density (vBMD) and bone geometry by quantitative computed tomography and relate these to circulating bio E2 and bio testosterone levels. DESIGN: We studied a cross-sectional, age-stratified population sample of 235 women (age, 21-97 yr). RESULTS: vBMD/structural parameters were not related to sex steroid levels in young premenopausal women (age, 20-39 yr) with a median bio E2 level of 17 pg/ml (63 pmol/liter). By contrast, bio E2 and bio testosterone levels were both significantly associated with trabecular and cortical vBMD and cortical area at multiple sites in late postmenopausal women (age > or = 60 yr) who had a median bio E2 level of 3 pg/ml (11 pmol/liter). Late premenopausal and early postmenopausal women (age, 40-59 yr) with an intermediate median bio E2 level of 11 pg/ml (42 pmol/liter) showed age-adjusted correlations of bio E2 levels with trabecular but not with cortical vBMD. CONCLUSIONS: In women, bio E2 levels are associated with vBMD and some structural bone parameters at low but not high bio E2 levels. Similar to findings in men, the threshold for estrogen deficiency in cortical bone in women appears to be lower than that in trabecular bone.

Adult↗

Imaging microscopy of the middle and inner ear: Part II: MR microscopy.

Anatomic definition of the membranous labyrinth in the clinical setting remains limited despite significant technological advances in magnetic resonance imaging (MRI). Recent developments in ultra-high resolution imaging for use in the research laboratory on small animals and pathologic specimens have given rise to the field of imaging microscopy. We have delineated for the first time the labyrinthine structures in a human temporal bone cadaver specimen using these novel techniques. This approach to the study of the middle and inner ear avoids tissue destruction inherent in histological preparations using standard light microscopy techniques. Part I of this series focused on bony middle and inner ear anatomy with MicrCT. In Part II, we present high-resolution MicroMR images to highlight the utility of this technique in teaching radiologists and otolaryngologists clinically relevant anatomy focusing on the membranous labyrinth. This anatomy can be further enhanced using 3D volume-rendered images. It is hoped that familiarity with these ex vivo anatomic techniques will encourage further developments in the field of high-resolution clinical imaging for patients with temporal bone pathologies.

Anatomy, Cross-Sectional↗

Schwarz meets Schwann: design and fabrication of biomorphic tissue engineering scaffolds.

Tissue engineering is a discipline at the leading edge of the field of computer assisted intervention. This multidisciplinary engineering science is based on the notion of design and fabrication of scaffolds- porous, three-dimensional "trellis-like" biomimetic structures that, on implantation, provide a viable environment to recuperate and regenerate damaged cells. Existing CAD-based approaches produce porous labyrinths with contra-naturam straight edges. The biomorphic geometry that mimics the secundam-naturam substrate would be one that is continuous through all space, partitioned into two not-necessarily-equal sub-spaces by a non-intersecting, two-sided surface. Minimal surfaces are ideal to describe such a space. We present results on the premier attempt in computer controlled fabrication and mechanical characterization of Triply Periodic Minimal Surfaces [TPMS]. This initiative is a significant step to link Schwann's 1838 cell theory with Schwarz's discovery of TPMS in 1865 to fabricate the previously elusive optimal biomorphic tissue analogs.

Biocompatible Materials↗

Examination of dosimetry accuracy as a function of seed detection rate in permanent prostate brachytherapy.

The variation of permanent prostate brachytherapy dosimetry as a function of seed detection rates was investigated for I125 implants with seed activities commonly employed in contemporary practice. Post-implant imaging and radiation dosimetry data from nine patients who underwent PPB served as the basis of this simulation study. One-thousand random configurations of detected seeds were generated for each patient dataset using various seed detection levels from 30% to 99%. Dose parameters, including D90, were computed for each configuration and compared with the actual dosimetry data. A total of 108 000 complete sets of post-PPB dose volume statistics were computed. The results demonstrated that although the average D90 differed from the true value by less than 5% when 70% or more seeds were identified, the D90 of an individual case could deviate up to 13%. The 95% confidence interval (CI) of estimated D90 values differ by less than 5% from the actual value when 95% or more seeds are detected, or approximately a 7 Gy difference in the D90 value for a prescription dose of 144 Gy. Estimated target volume dose parameters tended to decrease with reduced seed detection rates. The most variable dose parameter was the prostate V100 in absolute scale while the urethral V100 was most variable in a relative sense. Based on this comprehensive simulation study, it is suggested that 95% or more seeds need to be localized in order to provide an accurate estimation of dose parameters for contemporary iodine 125 permanent prostate brachytherapy.

Brachytherapy↗

Relationship of volumetric BMD and structural parameters at different skeletal sites to sex steroid levels in men.

UNLABELLED: In a population-based, cross-sectional study, we related age-associated changes in vBMD and in bone structural parameters to circulating bioavailable estradiol and testosterone levels in men. Associations between these bone mass/structural parameters and sex steroid levels were progressively stronger with age. Our previously postulated "threshold" for skeletal estrogen deficiency was most evident at cortical sites. INTRODUCTION: Serum sex steroids, particularly estrogen levels, are associated with bone mass in men, and previous work has suggested that there may be a "threshold" bioavailable estradiol (bio E(2)) level below which the male skeleton becomes estrogen deficient. However, previous studies addressing this issue have exclusively used DXA, which cannot separate trabecular from cortical bone or provide information on bone geometry or structure. MATERIALS AND METHODS: In an age-stratified population sample of 314 men (age, 22-91 years), we assessed volumetric BMD (vBMD) and bone geometry by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia and related these to circulating bio E(2) and bio testosterone (T) levels. RESULTS: Compared with young men (age, 20-39 years), middle-aged men (age, 40-59 years) had significantly lower bio T (-26%, p < 0.001) and bio E(2) (-9%, p = 0.038) levels, and these decreases were even greater in the elderly men (age > or = 60 years, -60% and -38% for bio T and bio E(2), respectively, p < 0.001 for both). Reflecting their intact gonadal status, vBMD/structural parameters were not related to sex steroid levels in young men, whereas bio E(2) levels were associated consistently with vBMD and variably with bone geometric parameters in the elderly men; middle-aged men showed associations with bio E(2) and bio T at some sites. At all cortical sites, vBMD was associated with bio E(2) at low (<30 pM, R = 0.27-0.41, p < 0.05-0.001) but not high (> or =30 pM, R = -0.003 to 0.12, p = not significant) levels; no such differences were evident at trabecular sites. CONCLUSIONS: In men, bio E(2) is the most consistent predictor of vBMD and some bone geometric variables as assessed by QCT. We also extend our previous findings on a possible "threshold" for skeletal estrogen deficiency by showing that this is most evident for cortical sites.

Adult↗

Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites.

UNLABELLED: In a population-based, cross-sectional study, we assessed age- and sex-specific changes in bone structure by QCT. Over life, the cross-sectional area of the vertebrae and proximal femur increased by approximately 15% in both sexes, whereas vBMD at these sites decreased by 39-55% and 34-46%, respectively, with greater decreases in women than in men. INTRODUCTION: The changes in bone structure and density with aging that lead to fragility fractures are still unclear. MATERIALS AND METHODS: In an age- and sex-stratified population sample of 373 women and 323 men (age, 20-97 years), we assessed bone geometry and volumetric BMD (vBMD) by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia. RESULTS: In young adulthood, men had 35-42% larger bone areas than women (p < 0.001), consistent with their larger body size. Bone area increased equally over life in both sexes by approximately 15% (p < 0.001) at central sites and by approximately 16% and slightly more in men at peripheral sites. Decreases in trabecular vBMD began before midlife and continued throughout life (p < 0.001), whereas cortical vBMD decreases began in midlife. Average decreases in trabecular vBMD were greater in women (-55%) than in men (-46%, p < 0.001) at central sites, but were similar (-24% and -26%, respectively) at peripheral sites. With aging, cortical area decreased slightly, and the cortex was displaced outwardly by periosteal and endocortical bone remodeling. Cortical vBMD decreased over life more in women ( approximately 25%) than in men (approximately 18%, p < 0.001), consistent with menopausal-induced increases in bone turnover and bone porosity. CONCLUSIONS: Age-related changes in bone are complex. Some are beneficial to bone strength, such as periosteal apposition with outward cortical displacement. Others are deleterious, such as increased subendocortical resorption, increased cortical porosity, and, especially, large decreases in trabecular vBMD that may be the most important cause of increased skeletal fragility in the elderly. Our findings further suggest that the greater age-related decreases in trabecular and cortical vBMD and perhaps also their smaller bone size may explain, in large part, why fragility fractures are more common in elderly women than in elderly men.

Adult↗

Imaging microscopy of the middle and inner ear: Part I: CT microscopy.

Anatomic definition of the middle ear and bony labyrinth in the clinical setting remains limited despite significant technological advances in computed tomography (CT). Recent developments in ultra-high resolution imaging for use in the research laboratory on small animals and pathologic specimens have given rise to the field of imaging microscopy. We have taken advantage of this technique to image a human temporal bone cadaver specimen to delineate middle ear and labyrinthine structures, only seen previously using standard light microscopy. This approach to the study of the inner ear avoids tissue destruction inherent in histological preparations. We present high-resolution MicroCT images of the middle ear and bony labyrinth to highlight the utility of this technique in teaching radiologists and otolaryngologists clinically relevant temporal bone anatomy. This study is not meant to function as a complete anatomic atlas of the temporal bone. We have selected several structures that are routinely delineated on clinical scanners to highlight the utility of imaging microscopy in displaying critical anatomic relationships in three orthogonal planes. These anatomic relationships can be further enhanced using 3D volume rendering.

Cadaver↗

Statistical assessment of regional time-density measurement of myocardial perfusion.

RATIONALE AND OBJECTIVES: The measurement of time-density relationships of the myocardium in studies of magnetic resonance perfusion images is a clinical technique used in assessing myocardial perfusion. This article presents a new technique, allowing regional time-density measurement and display of myocardial perfusion with improved accuracy compared with traditional manual trace techniques. Moreover, a method using statistical methods to discriminate relative decreased perfusion regions that differ significantly from the normally perfused myocardial tissue is introduced. MATERIALS AND METHODS: Human datasets were obtained using a 1.5 T Signa Echospeed system (GE Medical Systems, Milwaukee, WI). The perfusion sequence was a 2D cardiac-gated fast gradient echo sequence with echo train readout, generating an in-plane pixel size of 1.46 mm2. Seven 10-mm-thick contiguous short axis tomographic slice images were obtained during a prolonged single breathhold. Data was collected at 30 time phases per slice image level during passage of 20 cc gadolinium contrast injected at a rate of 4-5 cc/sec into an antecubital vein. RESULTS: Dilution properties can be determined and displayed as color-encoded regions superimposed on the myocardial slice according to the area of interest. Time-density curves throughout the perfusion study can be generated. Moreover, displays of normal and decreased perfusion areas can be used as statistically enhanced diagnosis guides. CONCLUSION: This measurement, display, and diagnosis technique adds diagnostically important information to previous measurement and visualization techniques, providing enhanced detection and quantitative evaluation of regional deficits in myocardial contractility and perfusion, providing improved reliability and reproducibility of clinical diagnoses from MR-perfusion data.

Analysis of Variance↗