Biomedical subjects

David Dean

Publications and source records attributed to David Dean.

At least 19 recordsLinked to original sources

PubMed2006

Quantifying degeneration of white matter in normal aging using fractal dimension.

Although degeneration of brain white matter (WM) in aging is a well-recognized problem, its quantification has mainly relied on volumetric measurements, which lack detail in describing the degenerative adaptation. In this study, WM structural complexity was evaluated in healthy old and young adults by analyzing the three-dimensional fractal dimension (FD) of WM segmented from magnetic resonance images of brain. FDs detected in the old were significantly smaller than in the young subjects. Specifically, WM interior structure complexity degenerated in the left hemisphere in old men but in the right hemisphere in old women. Men showed more complex WM patterns than women. An asymmetrical (right-greater-than-left-hemisphere) complexity pattern was observed in the interior and general structures of WM, yet the surface complexity was symmetrical across WM structures of the two hemispheres. WM volumes were also measured, but no significant decline was found with aging. These results suggest that the deterioration of WM complexity is not uniformly distributed between the genders and across brain hemispheres.

Adolescent↗

PubMed2005

A three-dimensional fractal analysis method for quantifying white matter structure in human brain.

Fractal dimension (FD) is increasingly used to quantify complexity of brain structures. Previous research that analyzed FD of human brain mainly focused on two-dimensional measurements. In this study, we developed a three-dimensional (3D) box-counting method to measure FD of human brain white matter (WM) interior structure, WM surface and WM general structure simultaneously. This method, which firstly incorporates a shape descriptor (3D skeleton) representing interior structure and combines the three features, provides a more comprehensive characterization of WM structure. WM FD of different brain segments was computed to test robustness of the method. FDs of fractal phantoms were computed to test the accuracy of the method. The consistency of the computed and theoretical FD values suggests that our method is accurate in measuring FDs of fractals. Statistical analysis was performed to examine sensitivity of the method in detecting WM structure differences in a number of young and old subjects. FD values of the WM skeleton and surface were significantly greater in young than old individuals, indicating more complex WM structures in young people. These results suggest that our method is accurate in quantifying three-dimensional brain WM structures and sensitive in detecting age-related degeneration of the structures.

Age Factors↗

PubMed2005

Pc 4 photodynamic therapy of U87-derived human glioma in the nude rat.

BACKGROUND AND OBJECTIVES: As a potential therapy for malignant glioma, we tested the phthalocyanine photosensitizer Pc 4 for: (1) rapid clearance from the vasculature, (2) specificity for glioma, and (3) tumoricidal photosensitizing capability. STUDY DESIGN/MATERIALS AND METHODS: Parenchymal injection of U87 cells into athymic rat brains (N = 100) was followed after 12 days by tail vein injection of 0.5 mg/kg Pc 4. After 1 day, the tumor was illuminated with either 5 (N = 11) or 30 (N = 16) J/cm(2) red light at 672 nm. Sacrifice was 1 day later. The brains from these 27 animals underwent H&E (necrosis) and TUNEL assay (apoptosis) histology. Pc 4 concentration of explanted brains and tumors (N = 16), and all blood samples (N = 52) were determined by HPLC-MS 1 day post Pc 4 administration. RESULTS: Tumor-specific apoptosis was almost uniformly seen; however, necrosis was found mostly in the high-light-dose group. Pc 4 concentration in bulk tumor averaged 3.8 times greater than in normal brain. CONCLUSIONS: These results warrant expanding this pre-clinical study to seek effective baseline Pc 4 drug- and light-doses and infusion-to-photoirradiation timing that would be necessary for a Pc 4-mediated PDT clinical trial for glioma patients.

Animals↗

PubMed2005

Is developing scientific thinking all about learning to control variables?

Academically low-performing urban sixth graders engaged in inquiry activity received a suggestion that they focus their investigation on the role of a single factor. This suggestion had significant effects on their use of a superficially dissimilar strategy--controlling the variation of other factors. This latter strategy has received the lion's share of attention in research on the development of scientific reasoning. These results have implications, we propose, for what undergoes development with respect to scientific thinking and how this development can best be facilitated.

Child↗

PubMed2005

A three-dimensional morphometric study of craniofacial shape in schizophrenia.

BACKGROUND: Subtle dysmorphogenesis of the craniofacial region constitutes important corroborating evidence of the neurodevelopmental origins of schizophrenia. Advances in facial visualization now allow for three-dimensional anthropometric evaluations of potentially greater discriminatory power in examining the complex geometric relationships of facial topography. METHOD: Sixty-five anthropometrically derived landmarks were identified from three-dimensional facial images collected from 14 patients with schizophrenia and 11 comparison subjects, imaged with a high-resolution, portable laser scanner. RESULTS: Using the Procrustes morphometric approach for shape analysis, the difference in mean shapes was highly significant, with patients exhibiting superoinferior elongation of the face. CONCLUSIONS: The topography of craniofacial anomalies in schizophrenia is not random and points to midline deformation.

Adult↗

PubMed2004

Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model.

In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion. To test this hypothesis, healing bone was investigated within a rabbit incisor extraction socket, a subcritical size bone defect that resists significant soft tissue invasion by virtue of its conformity. After removal of the incisor teeth, one tooth socket was left as an empty control, one was filled with crosslinked polymer networks formed from the hydrophobic polymer poly(propylene fumarate) (PPF), and one was filled with a hydrogel formed from the hydrophilic oligomer oligo(poly(ethylene glycol) fumarate) (OPF). At five different times (4 days as well as 1, 2, 4, and 8 weeks), jaw bone specimens containing the tooth sockets were removed. We analyzed bone healing by histomorphometrical analysis of hematoxylin and eosin stained sections as well as immunohistochemically stained sections. The proposed hypothesis, that a hydrophilic material would hinder bone healing, was supported by the histomorphometrical results. In addition, the immunohistochemical results reflect molecular signaling indicative of the early invasion of platelets, the vascularization of wound-healing tissue, the differentiation of migrating progenitor cells, and the formation and remodeling of bone tissue. Finally, the results emphasize the need to consider biomaterial properties and their differing effects upon endogenous growth factors, and thus bone healing, during the development of tissue engineering devices.

Animals↗

PubMed2004

Alternative forms of the Rey Auditory Verbal Learning Test: a review.

Practice effects in memory testing complicate the interpretation of score changes over repeated testings, particularly in clinical applications. Consequently, several alternative forms of the Auditory Verbal Learning Test (AVLT) have been developed. Studies of these typically indicate that the forms examined are equivalent. However, the implication that the forms in the literature are interchangeable must be tempered by several caveats. Few studies of equivalence have been undertaken; most are restricted to the comparison of single pairs of forms, and the pairings vary across studies. These limitations are exacerbated by the minimal overlapping across studies in variables reported, or in the analyses of equivalence undertaken. The data generated by these studies are nonetheless valuable, as significant practice effects result from serial use of the same form. The available data on alternative AVLT forms are summarized, and recommendations regarding form development and the determination of form equivalence are offered.

Humans↗

PubMed2003

Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth.

A novel approach to the manufacture of biodegradable polymeric scaffolds for tissue-engineering utilizing stereolithography (SLA) is presented. SLA is a three-dimensional (3D) printing method that uses an ultraviolet laser to photo-crosslink a liquid polymer substrate. The current generation of SLA devices provide a 3D printing resolution of 0.1 mm. The experiments utilized a biodegradable resin mixture of diethyl fumarate (DEF), poly(propylene fumarate) (PPF), and a photoinitiator, bisacylphosphine oxide (BAPO). The PPF is crosslinked with the use of the SLA's UV laser (325-nm wavelength). An SLA device was retrofitted with a custom fixture build tank enclosing an elevator-driven build table. A 3D prototype model testing the manufacturing control this device provides was created in a computer-aided-design package. The resulting geometric data were used to drive the SLA process, and a DEF/PPF prototype part was successfully manufactured. These scaffolds have application in the tissue engineering of bony substrates.

Biocompatible Materials↗

PubMed2003

Plug pattern optimization for gamma knife radiosurgery treatment planning.

PURPOSE: To develop a novel dose optimization algorithm for improving the sparing of critical structures during gamma knife radiosurgery by shaping the plug pattern of each individual shot. METHOD AND MATERIALS: We first use a geometric information (medial axis) aided guided evolutionary simulated annealing (GESA) optimization algorithm to determine the number of shots and isocenter location, size, and weight of each shot. Then we create a plug quality score system that checks the dose contribution to the volume of interest by each plug in the treatment plan. A positive score implies that the corresponding source could be open to improve tumor coverage, whereas a negative score means the source could be blocked for the purpose of sparing normal and critical structures. The plug pattern is then optimized via the GESA algorithm that is integrated with this score system. Weight and position of each shot are also tuned in this procedure. RESULTS: An acoustic tumor case is used to evaluate our algorithm. Compared to the treatment plan generated without plug patterns, adding an optimized plug pattern into the treatment planning process boosts tumor coverage index from 95.1% to 97.2%, reduces RTOG conformity index from 1.279 to 1.167, lowers Paddick's index from 1.34 to 1.20, and trims the critical structure receiving more than 30% maximum dose from 16 mm(3) to 6 mm(3). CONCLUSIONS: Automated GESA-based plug pattern optimization of gamma knife radiosurgery frees the treatment planning team from the manual forward planning procedure and provides an optimal treatment plan.

Algorithms↗

PubMed2003

Confined diffusion without fences of a g-protein-coupled receptor as revealed by single particle tracking.

Single particle tracking is a powerful tool for probing the organization and dynamics of the plasma membrane constituents. We used this technique to study the micro -opioid receptor belonging to the large family of the G-protein-coupled receptors involved with other partners in a signal transduction pathway. The specific labeling of the receptor coupled to a T7-tag at its N-terminus, stably expressed in fibroblastic cells, was achieved by colloidal gold coupled to a monoclonal anti T7-tag antibody. The lateral movements of the particles were followed by nanovideomicroscopy at 40 ms time resolution during 2 min with a spatial precision of 15 nm. The receptors were found to have either a slow or directed diffusion mode (10%) or a walking confined diffusion mode (90%) composed of a long-term random diffusion and a short-term confined diffusion, and corresponding to a diffusion confined within a domain that itself diffuses. The results indicate that the confinement is due to an effective harmonic potential generated by long-range attraction between the membrane proteins. A simple model for interacting membrane proteins diffusion is proposed that explains the variations with the domain size of the short-term and long-term diffusion coefficients.

Bacteriophage T7↗

PubMed2003

Poly(propylene fumarate) and poly(DL-lactic-co-glycolic acid) as scaffold materials for solid and foam-coated composite tissue-engineered constructs for cranial reconstruction.

This pilot study investigates the osseointegration of four types of critical-size (1.5-cm diameter) rabbit cranial defect (n = 35) bone graft scaffolds. The first is a solid poly(propylene fumarate)/beta-tricalcium phosphate(PPF/beta-TCP) disk; the three remaining constructs contain a PPF/beta-TCP core coated with a 1-mm resorptive porous foam layer of PPF or PLGA [poly(DL-lactic-co-glycolic acid)], and bone marrow. Animals were killed at 6, 12, and 20 weeks. There was no evidence of a foreign body inflammatory response at any time during the study. Histomorphometric analyses of new bone formation sorted lineal and areal measures of new bone into three cranial layers (i.e., external, middle, and internal). Statistical analyses revealed significantly more bone in the PLGA foam-coated constructs than in the PPF foam-coated constructs (p < 0.03). No implant fixation was used; there is no strength at time 0. Twenty percent of all explants were tested for incorporation strength with a one-point "push-in" test, and failure ranged from 8.3 to 34.7 lb. The results of this study support the use of PPF as a biocompatible material that provides both a structural and osteogenic substrate for the repair of cranial defects.

Animals↗

PubMed2003

Computer aided design of large-format prefabricated cranial plates.

The authors' objective in this project was to replace current state-of-the-art manual methods for preoperative production (i.e., prefabrication) of large-format (>100 cm2) cranioplasties with a system for computer-aided design and direct computer-aided manufacture of the implant's shape. This system uses standard 3D CT data, requires no specialized training, and produces an accurately fitting cranioplasty that can be recast in the physician's material of choice (e.g., polymethylmethacrylate [PMMA] or pre-bent titanium plating). The authors begin by locating the cranial defect margin on a skull surface image generated from a 3D head CT-scan. A right-to-left mirrored or average 3D skull surface template image is then fit to the patient's skull surface image. The area around the defect is cut out and stitched to the previously isolated defect margin. This defect-filling surface is then tapered and 3D printed. The 3D printed implant model is then recast in a biocompatible material. Manually generated cranial implants produced for five patients were compared with implants resulting from this new computer-based method. All five computer-generated implants were better fitting and more cosmetically suitable than the manually generated skull plates received by these patients. These well-fitting implants are more likely to protect the brain from trauma and infection. Therefore, the authors conclude that their new production method provides a better result with less expense than current methods for preoperative or intraoperative fabrication of large-format cranioplasties.

Adult↗

PubMed2003

Integration of neurosurgical image guidance and an intraoperative magnetic resonance scanner. The University Hospitals of Cleveland experience.

BACKGROUND: Intraoperative magnetic resonance (MR) imaging has been employed as an alternative to image guidance using preoperative images. We integrated both systems to evaluate their clinical use. METHODS: The BrainLAB VectorVision system was integrated in an intraoperative Siemens Open Viva 0.2-tesla MR system. Clinical experience was assessed. RESULTS: Patterns of intraoperative imaging emerged, and benefit was seen in registering preoperative and intraoperative images. CONCLUSIONS: This integrated system has clinically observed effects on imaging, navigation, and surgery.

Humans↗

PubMed2003

Effect of changing patient position from supine to prone on the accuracy of a Brown-Roberts-Wells stereotactic head frame system.

OBJECTIVE: Despite the growing popularity of frameless image-guided surgery systems, stereotactic frame systems are widely accepted by neurosurgeons and are commonly used to perform biopsies, functional procedures, and stereotactic radiosurgery. We investigated the accuracy of the Brown-Roberts-Wells stereotactic frame system when the mechanical load on the frame changes between preoperative imaging and the intervention because of different patient position: supine during imaging, prone during intervention. METHODS: We analyzed computed tomographic images acquired from 14 patients who underwent stereotactic biopsy, deep brain stimulator implantation, or radiosurgery. Two images were acquired for each patient, one with the patient in the supine position and one in the prone position. The prone images were registered to the respective supine images by use of an intensity-based registration algorithm, once using only the frame and once using only the head. The difference between the transformations produced by these two registrations describes the movement of the patient's head with respect to the frame. RESULTS: The maximum frame-based registration error between the supine and prone positions was 2.8 mm; it was more than 2 mm in two patients and more than 1.5 mm in six patients. Anteroposterior translation is the dominant component of the difference transformation for most patients. In general, the magnitude of the movement increased with brain volume, which is an index of head weight. CONCLUSION: To minimize frame-based registration error caused by a change in the mechanical load on the frame, stereotactic procedures should be performed with the patient in the identical position during imaging and intervention.

Brain Diseases↗

PubMed2002

Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model.

The treatment of large cranial defects may be greatly improved by the development of precisely formed bone tissue engineering scaffolds. Such scaffolds could be constructed by using UV laser stereolithography to photocrosslink a linear, biodegradable polymer into a three-dimensional implant. We have previously presented a method to photocrosslink the biodegradable polyester, poly(propylene fumarate) (PPF). To ensure the safety and effectiveness of this technique, the soft and hard tissue response to photocrosslinked PPF scaffolds of different pore morphologies was investigated. Four classes of photocrosslinked PPF scaffolds, constructed with differing porosities (57-75%) and pore sizes (300-500 or 600-800 microm), were implanted both subcutaneously and in 6.3-mm-diameter cranial defects in a rabbit model. The rabbits were sacrificed at 2 and 8 weeks, and the implants were analyzed by light microscopy, histological scoring analysis, and histomorphometric analysis. Results showed the PPF scaffolds elicit a mild tissue response in both soft and hard tissues. Inflammatory cells, vascularization, and connective tissue were observed at 2 weeks; a decrease in inflammatory cell density and a more organized connective tissue were observed at 8 weeks. Scaffold porosity and scaffold pore size were not found to significantly affect the observed tissue response. Evidence of scaffold surface degradation was noted both by histology and histomorphometric analysis. Bone ingrowth in PPF scaffolds implanted into cranial defects was <3% of the defect area. The results indicate that photocrosslinked PPF scaffolds are biocompatible in both soft and hard tissues and thus may be an attractive platform for bone tissue engineering.

Animals↗

PubMed2002

In vitro degradation and fracture toughness of multilayered porous poly(propylene fumarate)/beta-tricalcium phosphate scaffolds.

This study investigated the in vitro degradation of poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) scaffolds in pH 7.4 phosphate-buffered saline at 37 degrees C. Scaffold design consisted of three layers: two solid layers about a central layer of porous PPF foam. Solid PPF with molecular weights of 810 and 1450 Da was crosslinked under UV light. PPF foam was prepared by a photocrosslinking, porogen-leaching method with an initial porogen content of 80 wt % and two sizes, 150-300 and 300-500 microm. Comparison of initial and residual weights demonstrated a 14.3 +/- 2.0% loss of mass at 3 weeks and a 16.6 +/- 1.8% loss of mass at 6 weeks. Observed pH values for all constructs remained stable (7.15-7.40) throughout the 3 to 6 weeks. Scanning electron micrographs of these scaffolds revealed some loss of foam material between 3 and 6 weeks; however, foam microarchitecture was intact. Solid PPF fracture toughness was tested for high and low molecular weight PPF, 0.376 +/- 0.004 and 0.134 +/- 0.015 MPa(m)1/2, respectively. These values are roughly one magnitude less than human cortical bone.

Biomechanical Phenomena↗

PubMed2002

Bone formation in transforming growth factor beta-1-coated porous poly(propylene fumarate) scaffolds.

This study determined the bone growth into pretreated poly(propylene fumarate) (PPF) scaffolds implanted into a subcritical size, rabbit cranial defect. PPF scaffolds were constructed by using a photocrosslinking-porogen leaching technique. These scaffolds were then either prewetted (PPF-Pw), treated with RF glow-discharge (PPF-Gd), coated with fibronectin (PPF-Fn), or coated with rhTGF-beta1 (PPF-TGF-beta1). One of each scaffold type was then placed into the cranium of nine rabbits. The rabbits were sacrificed after 8 weeks, and the scaffolds were retrieved for histological analysis. The most bone formation was present in the PPF-TGF-beta1 implants; the newly formed bone had a trabecular appearance together with bone marrow-like tissue. Little or no bone formation was observed in implants without rhTGF-beta1. These histological findings were confirmed by image analysis. Bone surface area, bone area percentage, pore fill percentage, and pore area percentage were significantly higher in the rhTGF-beta1-coated implants than in the noncoated implants. No statistical difference was seen between the PPF-Fn, PPF-Pw, or PPF-Gd scaffolds for these parameters. Quadruple fluorochrome labeling showed that in PPF-TGF-beta1 implants bone formation mainly started in the interior of a pore and proceeded toward the scaffold. We conclude that (a) PPF-TGF-beta1 scaffolds can indeed adequately induce bone formation in porous PPF, and (b) PPF scaffolds prepared by the photocrosslinking-porogen leaching technique are good candidates for the creation of bone graft substitutes.

Animals↗

PubMed2002

Photocrosslinking characteristics and mechanical properties of diethyl fumarate/poly(propylene fumarate) biomaterials.

The development of tissue engineered materials for the treatment of large bone defects would provide attractive alternatives to the autografts, allografts, non-degradable polymers, ceramics, and metals that are currently used in clinical settings. To this end, poly(propylene fumarate) (PPF), a viscous polyester synthesized from diethyl fumarate (DEF), has been studied for use as an engineered bone graft. We have investigated the photocrosslinking of PPF dissolved in its precursor, DEF, using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and low levels of ultraviolet light exposure. A three factor, 2 x 2 x 4 factorial design was developed, studying the effects of PPF number average molecular weight, BAPO initiator content, and DEF content upon photocrosslinking characteristics and mechanical properties. Uncured DEF/PPF solution viscosity fell over three orders of magnitude as DEF content was increased from 0% to 75%. The exothermic photocrosslinking reaction released low levels of heat, with no more than 160J/g released from any formulation tested. As a result, the maximum photocrosslinking temperature remained below 47 degrees C for all samples. Both sol fraction and swelling degree generally increased with increasing DEF content. Compressive mechanical properties were within the range of trabecular bone, with the strongest samples possessing an elastic modulus of 195.3 +/- 17.5 MPa and a fracture strength of 68.8 +/- 9.4MPa. Finally, the results indicate that PPF crosslinking was facilitated at low DEF precursor concentrations, but hindered at higher precursor concentrations. These novel DEF/PPF solutions may be preferred over pure PPF as the basis for an engineered bone graft because they (1) exhibit reduced viscosity and thus are easily handled, (2) form polymer networks with compressive strength at fracture suitable for consideration for trabecular bone replacement, and (3) may be readily fabricated into solids with a wide range of structures.

Biocompatible Materials↗