A novel magnetic resonance imaging application to visualise and quantify the morphology of the synovial folds of the lateral atlanto-axial joints

Background: The synovial folds of the lateral atlanto-axial joints have not previously attracted significant radiological attention, being small and not routinely demonstrated on conventional MR images. However, they are considered to be a potential source of neck pain and disability, especially following whiplash injury. Purpose: The purpose of this study was to develop an imaging protocol and measurement technique to determine the normal morphology of the synovial folds in vivo and establish normative values for their dimensions. Methods: MR images of the cervical spine of 17 volunteers aged 20 to 50 years (mean 31.1, SD 5.9 years) were acquired using a 1.5T scanner. Seed growing and thresholding methods were used to identify the synovial folds and quantify their dimensions. Results: The median volume of the right ventral and right dorsal synovial folds was 92.01 mm3 and 76.44 mm3, respectively. Left ventral and left dorsal synovial fold median volume measured 79.26 mm3 and 56.44 mm3, respectively. There was a significant difference in volume between the ventral and dorsal synovial folds of the right and left lateral atlanto-axial joints (2(3)=17.54, P=.000). The test-retest reliability of the measurement technique was ICC 0.99 and the inter-examiner reliability ICC 0.80. Conclusion: This study is the first to establish a MR imaging protocol to visualise the synovial folds of the lateral atlanto-axial joints in vivo and quantify their morphology. The normative values established in the present study provide the basis for future studies to investigate the role of the synovial folds in patients with neck pain. <br/

Synovial folds of the lateral atlantoaxial joints:in vivo quantitative assessment using magnetic resonance imaging in healthy volunteers

Study design: analysis of magnetic resonance (MR) images of healthy volunteers.Objective: to develop and validate an imaging protocol and measurement technique to describe the morphology and quantify the dimensions of the synovial folds of the lateral atlantoaxial joints in vivo.Summary of background date: the synovial folds of the lateral atlantoaxial joints are considered to be a potential source of neck pain and headache, especially following whiplash injury. Until recently, it has not been possible to image the synovial folds in vivo and consequently their normal morphology is not fully understood.Methods: MR images of the cervical spine of 17 volunteers (4 male and 13 female) were acquired using a 1.5-tesla scanner. The morphology of the synovial folds at the lateral atlantoaxial joints was described and their presence determined. The volume and cross-sectional area of the ventral and dorsal synovial folds of the right and left lateral atlantoaxial joints were measured and compared. The relationship between the dimensions of the synovial folds and subject age was examined. Twenty synovial folds were measured twice by one observer and once by a second observer for the determination of measurement reliability.Results: there was a significant difference in volume (chi [3] = 17.54, P = 0.000) and cross-sectional area (chi [3] = 18.95, P = 0.000) between the ventral and dorsal synovial folds of the left and right lateral atlantoaxial joints. There was no correlation between synovial fold dimensions and age. The reliability of the measurements ranged from intraclass correlation coefficient 0.95 to 0.99 (intraobserver reliability) and intraclass correlation coefficients 0.75 to 0.82 (interobserver reliability).Conclusion: MR imaging was successfully implemented as a noninvasive method for visualizing the synovial folds of the lateral atlantoaxial joints and quantifying their dimensions in healthy volunteers. The results of this study provide a basis for future studies investigating synovial fold pathology in patients with neck pain and headache

Manual 768 or 384 well microplate gel 'dry' electrophoresis for PCR checking and SNP genotyping

Electrophoresis continues to be a mainstay in molecular genetic laboratories for checking, sizing and separating both PCR products, nucleic acids derived from in vivo or in vitro sources and nucleic acid–protein complexes. Many genomic and genetic applications demand high throughput, such as the checking of amplification products from many loci, from many clones, from many cell lines or from many individuals at once. These applications include microarray resource development and expression analysis, genome mapping, library and DNA bank screening, mutagenesis experiments and single nucleotide polymorphism (SNP) genotyping. PCR hardware compatible with industry standard 96 and 384 well microplates is commonplace. We have previously described a simple system for submerged horizontal 96 and 192 well polyacrylamide or agarose microplate array diagonal gel electrophoresis (MADGE) which is microplate compatible and suitable for PCR checking, SNP typing (restriction fragment length polymorphism or amplification refractory mutation system), microsatellite sizing and identification of unknown mutations. By substantial redesign of format and operations, we have derived an efficient ‘dry’ gel system that enables direct 96 pin manual transfer from PCR or other reactions in microplates, into 768 or 384 well gels. Combined with direct electrode contact in clamshell electrophoresis boxes which plug directly to contacts in a powered stacking frame and using 5–10 min electrophoresis times, it would be possible (given a sufficient supply of PCRs for examination) for 1 million gel tracks to be run per day for a minimal hardware investment and at minimal reagent costs. Applications of this system for PCR checking and SNP genotyping are illustrated. <br/

Synovial folds - a pain in the neck?

The synovial folds of the cervical spine are regarded as a potential source of neck pain and headache, especially following whiplash injury. Damage to the synovial folds following motor vehicle trauma has been well documented in post-mortem studies. However, methods of identifying injury to the synovial folds in the survivors of motor vehicle trauma have proven elusive to date. Recently, it has been made possible to image the synovial folds in vivo using magnetic resonance imaging. This now makes it feasible to investigate the potential involvement of synovial folds in the generation of neck pain and headache and its relief using spinal manipulation. This paper reviews critically the morphology of the synovial folds of the cervical spine that underpins the hypotheses proposed to explain their functional and clinical significance and a new system of naming and classifying the synovial folds is presented. Although there is some evidence to support the contribution of the synovial folds to neck pain, several theories have little or no support and require investigation and further evaluation. These findings have implications for understanding the anatomical basis of neck pain and headache and the rationale for the use of spinal manipulation in their management.<br/

Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and demonstration of the potential to identify severe, moderate, silent, rare, and paucimorphic mutations in the general population

We have developed a mutation-scanning approach suitable for whole population screening for unknown mutations. The method, meltMADGE, combines thermal ramp electrophoresis with MADGE to achieve suitable cost efficiency and throughput. The sensitivity was tested in blind trials using 54 amplicons representing the BRCA1 coding region and a panel of 94 unrelated family breast cancer risk consultands previously screened in a clinical diagnostic laboratory. All 10 common polymorphisms, 15/15 previously identified disease-causing mutations, and three previously untested single base changes were identified. Assays of LDLR exons 3 and 8 were validated in 460 familial hypercholesteremics and detected 8/9 known variants. We then applied the exon 3 assay in several DNA banks representing 8000 subjects with known cholesterol values and applied both assays in one DNA bank (n = 3600). In exon 3 we identified one previously reported moderate mutation, P84S (n = 1), also associated with moderate hypercholesteremia in this subject; an unreported silent variant, N76N (n = 1); and known severe hypercholesteremia splice mutation 313+1GA (n = 2). Around exon 8 we identified a paucimorphism (n = 35) at the splice site 1061–8TC (known to be in complete linkage disequilibrium with T705I) and unreported sequence variants 1186+11GA (n = 1) and D335N GA (n = 1). The cholesterol value for D335N was on the 96.2 percentile and for T705I, 2/35 carriers were above the 99th percentile. Thus, variants with predicted severe, moderate, and no effect were identified at the population level. In contrast with case collections, CpG mutations predominated. MeltMADGE will enable definition of the full population spectrum of rare, paucimorphic, severe, moderate (forme fruste), and silent mutations and effects

Morphometry of the synovial folds of the lateral atlanto-axial joints: the anatomical basis for understanding their potential role in neck pain

Purpose: intra-articular synovial folds of the cervical spine are considered to be a potential source of neck pain and disability. The purpose of the present study was to devise and validate a method to determine the normal morphometry of the synovial folds as a basis for understanding their functional and clinical significance.Methods: nine cadaver cervical spines were sectioned in the sagittal plane. The presence of the synovial folds at the lateral atlanto-axial joints was determined and their morphology described. Depth of projection, cross-sectional area and volume of the ventral and dorsal synovial folds of the right and left lateral atlanto-axial joints were measured from sagittal sections and compared. The relationship between synovial fold dimensions and subject age and cartilage degeneration were determined. Repeat measurements were made for the calculation of method reliability, and the water displacement method was used to determine method validity.Results: there was a trend for ventral synovial folds to be larger than dorsal synovial folds. There was no correlation between synovial fold dimensions and age and extent of cartilage degeneration. Measurement reliability ranged from intraclass correlation coefficient 0.95–1.00 (intra-observer), 0.95–1.00 (test–retest) and 0.61–1.00 (inter-observer). Limits of agreement for the sectional and water displacement methods for the measurement of synovial fold volume were ?1.04 ± 3.35 mm3.Conclusions: a reliable method for quantifying synovial fold dimensions was devised. The results of this study provide a basis for the determination and diagnosis of pathologies affecting the synovial fold

The influence of age, anthropometrics and range of motion on the morphometry of the synovial folds of the lateral atlanto-axial joints: a pilot study

The purpose of this study was to investigate the effect of age, anthropometrics and cervical range of motion upon synovial fold volume. Ten healthy female subjects aged 20-40 years were included in the study. Age, height, body mass, dimensions of the head and neck and cervical range of motion of each subject were measured. Magnetic resonance (MR) images of the cervical spine were acquired; the volume of the ventral and dorsal synovial folds of the right and the left lateral atlanto-axial joints was measured using seed growing and thresholding methods. Using Spearman's correlation coefficient, it was determined that there was no correlation between synovial fold volume and age. Synovial fold volume was positively correlated with subject height and neck length but negatively correlated with body mass, body mass index and the circumference of the head and neck. The relationship between synovial fold volume and range of cervical motion varied with the plane of movement. The ability to image the synovial folds of the lateral atlanto-axial joints using MR imaging to determine their normal morphology provides the basis for investigating synovial fold pathology in patients with neck pain and headache