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Biomedical subjects

David R Haynor

Publications and source records attributed to David R Haynor.

11 recordsLinked to original sources
PubMed2006

Pathway and gene-set activation measurement from mRNA expression data: the tissue distribution of human pathways.

BACKGROUND: Interpretation of lists of genes or proteins with altered expression is a critical and time-consuming part of microarray and proteomics research, but relatively little attention has been paid to methods for extracting biological meaning from these output lists. One powerful approach is to examine the expression of predefined biological pathways and gene sets, such as metabolic and signaling pathways and macromolecular complexes. Although many methods for measuring pathway expression have been proposed, a systematic analysis of the performance of multiple methods over multiple independent data sets has not previously been reported. RESULTS: Five different measures of pathway expression were compared in an analysis of nine publicly available mRNA expression data sets. The relative sensitivity of the metrics varied greatly across data sets, and the biological pathways identified for each data set are also dependent on the choice of pathway activation metric. In addition, we show that removing incoherent pathways prior to analysis improves specificity. Finally, we create and analyze a public map of pathway expression in human tissues by gene-set analysis of a large compendium of human expression data. CONCLUSION: We show that both the detection sensitivity and identity of pathways significantly perturbed in a microarray experiment are highly dependent on the analysis methods used and how incoherent pathways are treated. Analysts should thus consider using multiple approaches to test the robustness of their biological interpretations. We also provide a comprehensive picture of the tissue distribution of human gene pathways and a useful public archive of human pathway expression data.

Cell Line↗
PubMed2006

Intravascular hematocrit layering in equilibrium phase contrast-enhanced MR angiography of the peripheral vasculature.

PURPOSE: To evaluate intravenous hematocrit (HCT) layering detected in patent calf veins that potentially simulate filling defects seen in deep venous thrombosis (DVT). MATERIALS AND METHODS: Flow characteristics, vessel size, and enhancement patterns of veins with HCT layering were examined and compared with those of normal veins in vivo. Ex vivo studies were conducted with conventional and blood pool contrast agents to study the effects of MRI parameters and intrinsic variables on detecting HCT layering. RESULTS: HCT layering was detected in high resolution equilibrium phase images in one of six healthy subjects, and five of five patients with peripheral vascular occlusive disease (PVOD). Layering occurred only in deep veins that had significantly slower flow and larger diameter (P < 0.001) compared to normal veins. Enhancement patterns observed in vivo were similar to those found in the ex vivo study. CONCLUSION: The HCT layering effect in MR venography has not been previously reported, likely because delayed equilibrium phase venous imaging is not frequently performed. The use of blood pool contrast agents and high resolution equilibrium phase imaging allows intravascular HCT layering to be observed within a 30-60-minute time frame. Several imaging characteristics that distinguish HCT layering from DVT are discussed.

Adult↗
PubMed2006

Transcranial Doppler grading criteria for basilar artery vasospasm.

OBJECTIVE: Transcranial Doppler (TCD) criteria for basilar artery (BA) vasospasm are poorly defined, and grading criteria for vertebrobasilar vasospasm are unavailable. The purpose of the present study was to define TCD grading criteria for BA vasospasm on the basis of the absolute flow velocities and the intracranial to extracranial flow velocity ratios for the posterior circulation, and to improve the sensitivity and specificity of TCD for diagnosis of BA vasospasm. METHODS: One hundred twenty-three patients with aneurysmal subarachnoid hemorrhage underwent 144 cerebral arteriograms with views of the BA during the acute phase of vasospasm (Days 3-14 after hemorrhage). BA diameters were measured and compared with diameters obtained from baseline arteriograms. Both BA and extracranial vertebral artery flow velocities were measured by TCD within 4 hours before the arteriogram. RESULTS: The velocity ratio between the BA and the extracranial vertebral arteries (VA) strongly correlated with the degree of BA narrowing (r2 = 0.648; P < 0.0001). A ratio higher than 2.0 was associated with 73% sensitivity and 80% specificity for BA vasospasm. A ratio higher than 2.5 with BA velocity greater than 85 cm/s was associated with 86% sensitivity and 97% specificity for BA narrowing of more than 25%. A BA/VA ratio higher than 3.0 with BA velocities higher than 85 cm/s was associated with 92% sensitivity and 97% specificity for BA narrowing of more than 50%. CONCLUSION: The BA/VA ratio improves the sensitivity and specificity of TCD detection of BA vasospasm. On the basis of the BA/VA ratio and BA mean velocities, we suggest new TCD grading criteria for BA vasospasm.

Adult↗
PubMed2005

A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment for depression has shown statistically significant effects, but the clinical significance of these effects has been questioned. METHODS: Patients with medication-resistant depression were randomized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110% the estimated prefrontal cortex threshold. Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end point was treatment response defined as a >or=50% decrease in Hamilton Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS: The response rate for the TMS group was 30.6% (11/35), significantly (p = .008) greater than the 6.1% (2/33) rate in the sham group. The remission rate for the TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33) rate in the sham group. The HDRS scores showed a significantly (p < .002) greater decrease over time in the TMS group compared with the sham group. CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and clinically significant antidepressant effects in patients with medication-resistant major depression.

Adult↗
PubMed2005

Three-year incidence of low back pain in an initially asymptomatic cohort: clinical and imaging risk factors.

STUDY DESIGN: Prospective cohort study of randomly selected Veterans Affairs out-patients without baseline low back pain (LBP). OBJECTIVE: To determine predictors of new LBP as well as the 3-year incidence of magnetic resonance imaging (MRI) findings. SUMMARY OF BACKGROUND DATA: Few prospective studies have examined clinical and anatomic risk factors for the development of LBP, or the incidence of new imaging findings and their relationship to back pain onset. METHODS: We randomly selected 148 Veterans Affairs out-patients (aged 35 to 70) without LBP in the past 4 months. We compared baseline and 3-year lumbar spine MRI. Using data collected every 4 months, we developed a prediction model of back pain-free survival. RESULTS: After 3 years, 131 subjects were contacted, and 123 had repeat MRI. The 3-year incidence of pain was 67% (88 of 131). Depression had the largest hazard ratio (2.3, 95% CI = 1.2-4.4) of any baseline predictor of inci-dent back pain. Among baseline imaging findings, central spinal stenosis and nerve root contact had the highest, though nonsignificant, hazard ratios. We did not find an association between new LBP and type 1 endplate changes, disc degeneration, annular tears, or facet degeneration. The incidence of new MRI findings was low, with the most common new finding being disc signal loss in 11 (9%) subjects. All five subjects with new disc extrusions and all four subjects with new nerve root impingement had new pain. CONCLUSION: Depression is an important predictor of new LBP, with MRI findings likely less important. New imaging findings have a low incidence; disc extrusions and nerve root contact may be the most important of these findings.

Adult↗
PubMed2004

Parametric shape modeling using deformable superellipses for prostate segmentation.

Automatic prostate segmentation in ultrasound images is a challenging task due to speckle noise, missing boundary segments, and complex prostate anatomy. One popular approach has been the use of deformable models. For such techniques, prior knowledge of the prostate shape plays an important role in automating model initialization and constraining model evolution. In this paper, we have modeled the prostate shape using deformable superellipses. This model was fitted to 594 manual prostate contours outlined by five experts. We found that the superellipse with simple parametric deformations can efficiently model the prostate shape with the Hausdorff distance error (model versus manual outline) of 1.32 +/- 0.62 mm and mean absolute distance error of 0.54 +/- 0.20 mm. The variability between the manual outlinings and their corresponding fitted deformable superellipses was significantly less than the variability between human experts with p-value being less than 0.0001. Based on this deformable superellipse model, we have developed an efficient and robust Bayesian segmentation algorithm. This algorithm was applied to 125 prostate ultrasound images collected from 16 patients. The mean error between the computer-generated boundaries and the manual outlinings was 1.36 +/- 0.58 mm, which is significantly less than the manual interobserver distances. The algorithm was also shown to be fairly insensitive to the choice of the initial curve.

Algorithms↗
PubMed2003

PET-CT image registration in the chest using free-form deformations.

We have implemented and validated an algorithm for three-dimensional positron emission tomography transmission-to-computed tomography registration in the chest, using mutual information as a similarity criterion. Inherent differences in the two imaging protocols produce significant nonrigid motion between the two acquisitions. A rigid body deformation combined with localized cubic B-splines is used to capture this motion. The deformation is defined on a regular grid and is parameterized by potentially several thousand coefficients. Together with a spline-based continuous representation of images and Parzen histogram estimates, our deformation model allows closed-form expressions for the criterion and its gradient. A limited-memory quasi-Newton optimization algorithm is used in a hierarchical multiresolution framework to automatically align the images. To characterize the performance of the method, 27 scans from patients involved in routine lung cancer staging were used in a validation study. The registrations were assessed visually by two expert observers in specific anatomic locations using a split window validation technique. The visually reported errors are in the 0- to 6-mm range and the average computation time is 100 min on a moderate-performance workstation.

Algorithms↗
PubMed2002

Ultrasonography and fluoroscopic fusion for prostate brachytherapy dosimetry.

PURPOSE: To investigate the feasibility of performing postimplant and intraoperative dosimetry for prostate brachytherapy by fusing transrectal ultrasound (TRUS) and fluoroscopic data. METHODS AND MATERIALS: Registration of ultrasound (prostate boundary) and fluoroscopic (seed) data requires spatial markers that are detectable by both imaging modalities. In this study, the needle tips were considered as such fiducials. Prostate phantoms were implanted with the seeds, and four localization needles were inserted. In the TRUS frame of reference, the longitudinal coordinate of the needle tip was determined by advancing the needle until the echo from its tip just registered at a known probe depth. The tip's transverse coordinates were determined from the associated TRUS slice. The three-dimensional needle tip positions were also calculated in the fluoroscopic coordinate system using a seed reconstruction method. The transformation between the TRUS and fluoroscopy coordinate systems was established by the least-squares solution using the singular value decomposition. RESULTS: With three of four needle tips as fiducials and the one remaining needle as a test target, the mean fiducial registration error was 0.8 mm and the test target registration error was 2.5 mm. When all four points were used for registration, the errors decreased to 1.1 mm. A comparison between the proposed method and CT-based dosimetry yielded a percentage of prostate volume receiving 100% and 150% of the prescribed minimal peripheral dose and minimal dose received by 90% of the prostate gland that agreed within 0.4%, 2.7%, and 4.2%, respectively. CONCLUSION: The combination of TRUS and fluoroscopy is a feasible alternative to the currently used CT-based postimplant dosimetry. Furthermore, because of online imaging capability, the method lends itself to real-time intraoperative applications.

Brachytherapy↗
PubMed2002

Transcriptome analysis of Escherichia coli using high-density oligonucleotide probe arrays.

Microarrays traditionally have been used to analyze the expression behavior of large numbers of coding transcripts. Here we present a comprehensive approach for high-throughput transcript discovery in Escherichia coli focused mainly on intergenic regions which, together with analysis of coding transcripts, provides us with a more complete insight into the organism's transcriptome. Using a whole genome array, we detected expression for 4052 coding transcripts and identified 1102 additional transcripts in the intergenic regions of the E.coli genome. Further classification reveals 317 novel transcripts with unknown function. Our results show that, despite sophisticated approaches to genome annotation, many cellular transcripts remain unidentified. Through the experimental identification of all RNAs expressed under a specific condition, we gain a more thorough understanding of all cellular processes.

3' Untranslated Regions↗
PubMed2002

Identifying operons and untranslated regions of transcripts using Escherichia coli RNA expression analysis.

Microarrays traditionally have been used to assay the transcript expression of coding regions of genes. Here, we use Escherichia coli oligonucleotide microarrays to assay transcript expression of both open reading frames (ORFs) and intergenic regions. We then use hidden Markov models to analyse this expression data and estimate transcription boundaries of genes. This approach allows us to identify 5' untranslated regions (5' UTRs) of transcripts as well as genes that are likely to be operon members. The operon elements we identify correspond to documented operons with 99% specificity and 63% sensitivity. Similarly we find that our 5' UTR results accurately coincide with experimentally verified promoter regions for most genes.

5' Untranslated Regions↗