Advances in Magnetic Resonance Imaging for the assessment of degenerative disc disease of the lumbar spine
From: Semin Spine Surg. 2007 June; 19(2): 65–71
The intervertebral disc is characterized by a tension-resisting annulus fibrosus, and a compression-resisting nucleus pulposus composed largely of proteoglycan. Both the annulus and the nucleus function in concert to provide the disc with mechanical stability. Early disc degeneration begins in the nucleus with proteoglycan depletion. Quantitative MRI techniques have been developed to non-invasively quantify the earliest degenerative changes that occur within the disc. Our ability to identify and quantify these early biochemical changes will provide a better understanding of the pathophysiology of disc degeneration and facilitate the study of interventions that aim to halt or reverse the degenerative process.
Degenerative disc disease of the intervertebral disc is the most common cause of back-related disability among North American adults. This sometimes debilitating condition affects nearly 12 million people in the United States, and may generate direct and indirect costs exceeding 50 billion dollars annually in health-related expenditures. The radiographic evaluation of patients with degenerative disc disease often begins with plain film radiography and a standard T1- and T2-weighted MRI to assess for structural changes within the nucleus and annulus indicative of disc degeneration including a loss of T2-weighted MRI signal, loss of disc height, disc bulge or herniation, posterior element arthrosis, stenosis, and potential vertebral body compromise. While standard MRI is able to detect these later stage developments, it is not able to provide a quantitative measure of the early changes that characterize early degenerative disc disease. This limitation has led to the search for quantitative, non-invasive measures to evaluate the earliest changes involved in the initiation of the degenerative cascade. Such an imaging tool will be important for the evaluation of the patients with early degenerative disc disease, and also in the assessment of disc regenerative or restorative technologies that aim to halt or reverse the degenerative process.
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Caveolin-1 expression and stress induced premature senescence in human intervertebral disc degeneration
From: Arthritis Res Ther. 2008 Aug 5;10(4):R87 [Epub ahead of print]
Chronic and debilitating low back pain is a common condition and a huge economic burden. Many cases are attributed to age related degeneration of the intervertebral disc, however, age related degeneration appears to occur at an accelerated rate in some individuals. We have previously demonstrated biomarkers of cellular senescence within the human intervertebral disc and suggested a role for senescence in intervertebral disc degeneration. Senescence occurs with ageing, but can also occur prematurely in response to stress. We hypothesised that stress induced premature senescence occurs within the intervertebral disc and here we have investigated the expression and production of caveolin-1, a protein that has been shown previously to be upregulated in stress induced premature senescence.
Caveolin-1 gene expression in human nucleus pulposus cells was assessed by conventional and quantitative real-time PCR and caveolin-1 protein expression examined within human intervertebral discs using immunohistochemistry. Correlation between caveolin-1 and p16INK4a biomarker of cellular senescence gene expression was investigated using quantitative real-time PCR.
Caveolin-1 gene and protein expression were demonstrated within the human intervertebral disc for the first time. Nucleus pulposus cells from degenerate discs exhibited elevated levels of caveolin-1 that did not relate to increasing chronological age. A negative correlation was observed between gene expression for caveolin-1 and donor age and no correlation was found between caveolin-1 protein expression and age. A positive correlation was identified between gene expression of caveolin-1 and biomarker of cellular senescence.
Our findings are consistent with a role for caveolin-1 in degenerative rather than age induced changes in the nucleus pulposus. Its expression in intervertebral disc tissue and its association with the senescent phenotype suggests that caveolin-1 and stress induced premature senescence may play a prominent role in the pathogenesis of intervertebral disc degeneration.
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Painful Disc Lesion: Can Modern Biplanar Magnetic Resonance Imaging Replace Discography?
From: J Spinal Disord Tech 2008; 21:430–435
Internal disc disruption’’ is one of the prominent somatic sources of low back pain. MRI is the most common investigation performed to evaluate discogenic pain. Though MRI has advantages of being a sensitive investigation for identifying pathologic anatomy of disc degeneration, its value is limited by its inability to evaluate the physiologic status of the disc. Studies have questioned the specificity of MRI in diagnosing discogenic pain and have reported degenerative changes in 26% to 57% of asymptomatic volunteers. Discography is a useful tool to identify the painful disc responsible for patient’s symptoms. In evaluation of discogenic low back pain there has been a debate as to whether discography should replace MRI. Proponents of discography believe that it is an invaluable tool for identifying the pathologic disc producing pain. Critics believe that discography is an invasive investigation and has no place in modern practice.
Over the last decade there has been a vast improvement in the quality of MR images. Attempts have been made to identify features on MRI scans that would correlate with patient’s symptoms and would potentially eliminate the need for discography. Such features are the vertebral end plate changes described by Modic and the high intensity zone described by Aprill and Bogduk. The implications of these findings have been a subject of controversy.
This is a prospective study aimed at correlating the results of discography with new MRI classification in a consecutive series of patients with disabling low back pain considered for spinal surgery. In addition, we also aimed to compare vertebral end plate changes and high intensity zones seen on MRI with discography findings.
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Characterization of intervertebral disc aging: longitudinal analysis of a rabbit model by magnetic resonance imaging, histology, and gene expression
From: Spine. 2008 Aug 1;33(17):1821-8.
A cohort of young, healthy New Zealand White rabbits was followed longitudinally with serial magnetic resonance imaging analysis and terminal analysis of histologic changes and gene expression to examine the changes observed during normal aging in the intervertebral disc. Although there is a correlation between aging and the onset of intervertebral disc degeneration, evidence suggests that distinct pathways are involved in these processes. Our group has characterized a reproducible rabbit model of intervertebral disc degeneration by magnetic resonance imaging, radiograph, histology, and mRNA expression. However, no similar analysis has been performed longitudinally for intervertebral disc aging to allow comparison of these 2 important processes.
Four skeletally mature female NZW rabbits were housed for 122 weeks, and lumbar spine MRIs were characterized serially. Histologic and quantitative gene expression analysis of the nucleus pulposus of these aging animals was performed, and compared with adult and young rabbits. Mean magnetic resonance imaging index decreased by <25% through 120 weeks. The histologic analysis showed changes in cell composition, with abundant notochordal cells in the young, chondrocyte-like cells and notochordal cells in the adult, and clusters of hypertrophic chondrocytes in the aging discs. The PCR analysis of the nucleus pulposus showed that gene expression of collagen decreased, whereas that for proteoglycans increased with aging. BMP-2, TIMP-1, and SOX-9 expression was significantly lower in the young compared with adult discs and TGF-beta1 demonstrated lower gene expression in young and aging animals.
Although dramatic cellular changes were observed, age-related magnetic resonance imaging changes occurred in this rabbit model of normal aging at a much slower rate than in a previous injury model of degeneration. In addition, the gene expression analysis of the nucleus pulposus demonstrated remarkable differences between aging and injury induced degeneration. These results suggest that aging and injury contribute uniquely to the process of intervertebral disc degeneration.
Lumbar disc degeneration: association between osteophytes, end-plate sclerosis and disc space narrowing
From: Annals of the Rheumatic Diseases 2007;66:330-333
Peripheral joint osteoarthritis is characterised radiologically by the presence of osteophytes, subchondral sclerosis and joint space narrowing. Joint space narrowing is due to cartilage loss, whereas both subchondral sclerosis and osteophytes are hypertrophic responses of bone, thought to arise directly either to cartilage loss or to biomechanical stress. The pathophysiology and hence the inter-relationship of these features are however not well understood. Recently, strong associations between the presence of enthesophytes, osteophytes and bone sclerosis at various joint sites have been shown. Partly on the basis of these observations, it has been suggested that some individuals may be more likely to develop bone formation in response to disease occurrence. We looked at a series of lumbar spine radiographs and characterised the severity of the component radiographic features. Although the pathology of disc degeneration differs from peripheral joint osteoarthritis, we hypothesised that if there was a predisposition to develop new bone formation in the form of osteophyte or sclerosis in response to mechanical stress, there would be a strong association between increasing severity of the features of new bone formation. The aim of this study was to determine the strength of the association between increasing severity of osteophytes and end-plate sclerosis, and the association between both these features and disc space narrowing in the lumbar spine.
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MRI follow-up of subchondral signal abnormalities in a selected group of chronic low back pain patients
From: Eur Spine J. 2008 Jul 22; [Epub ahead of print]
Subchondral signal abnormalities have been suggested to play an important role in chronic low back pain syndromes. Their natural course is not well known. In this study the morphology and natural course of isolated subchondral signal abnormalities in the lumbosacral spine were analyzed with MRI. Twenty-four chronic low back pain patients with a subchondral hypointensity on T1-weighted image (hyperintense on T2), indicating edema, were selected from a base population of 1,015 consecutive low back pain patients to a follow-up MRI study within 18-72 months. Exclusion criteria were age >60 years, nerve root compression, a more specific back disease or a recent or major spine operation. The size and location of each subchondral signal abnormality and endplate lesion and the degree of degenerative disc changes were evaluated and compared between the baseline and follow-up studies. Most subchondral hypointensities were found at the L4/L5 or L5/S1 disc space, anteriorly and in both adjacent endplates. Almost all (53/54) hypointensities were associated with an endplate lesion. Twelve of the 54 subchondral hypointensities enlarged, six remained constant and 36 decreased or disappeared while five new ones appeared. Twenty-two (41%) hypointensities changed totally to hyperintensities or to mixed lesions. If the hypointensity increased, decreased or changed into hyperintensity, a change tended to develop in the adjacent endplate. If the hypointensity was absent or unchanged, endplate lesions did not tend to progress. In the absence of disc herniation or other specific spinal disease, subchondral hypointensities indicating edema are uncommon. They seem to have a highly variable course. There appears to be a link between endplate lesions and subchondral signal abnormalities. Further study is needed to explain the contribution of these findings to low back symptoms.
