Different Load-Induced Alterations in Intervertebral Discs Between Low Back Pain Patients and Controls: A T2-map Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Investigate load-induced effects in lumbar intervertebral discs (IVDs) and differences between low back pain (LBP) patients and controls. SUMMARY OF BACKGROUND DATA: T2-map values, obtained from quantitative MRI sequences, reflect IVD tissue composition and integrity. Feasibility studies with T2-mapping indicate different load-induced effects in entire IVDs and posterior IVD parts between LBP patients and controls. Larger studies are required to confirm these findings and increase the understanding of specific characteristics distinguishing IVD changes in LBP patients compared with controls. MATERIALS AND METHODS: Lumbar IVDs of 178 patients (mean age: 43.8 yr; range: 20-60 yr) with >3 months of LBP and 74 controls (mean age: 40.3 yr; range: 20-60 yr) were imaged with T2-map sequence in a 3T scanner in supine position without axial load, immediately followed by a repeated examination, using the same sequence, with axial load. On both examinations, mean T2-map values were obtained from entire IVDs and from central/posterior IVD parts on the three midsagittal slices in 855 patient IVDs and 366 control IVDs. Load-induced effect was compared with Fold-change ratio and adjusted for IVD-degeneration grade. RESULTS: Loading induced an increase in T2-map values in both patients and controls. Excluding most extreme values, the ranges varied between -15% and +35% in patients and -11% and +36% in controls (first to 99th percentile). Compared with controls, the T2-map value increase in patients was 2% smaller in entire IVDs (Fold-change: 0.98, P =0.031), and for central and posterior IVD parts 3% (Fold-change: 0.98, P =0.005), respectively, 2% (Fold-change: 0.9, P =0.015) smaller. CONCLUSIONS: This quantitative study confirmed diverse load-induced behaviors between LBP patients and controls, suggesting deviant biomechanical characteristics between IVDs in patients and controls not only attributed to the global grade of degeneration. These findings are an important step in the continuous work of identifying specific IVD phenotypes for LBP patients. LEVEL OF EVIDENCE: Level II.

Texture Analysis of Magnetic Resonance Images Enables Phenotyping of Potentially Painful Annular Fissures.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To investigate whether intervertebral disc (IVD) image features, extracted from magnetic resonance (MR) images, can depict the extension and width of annular fissures and associate them to pain. SUMMARY OF BACKGROUND DATA: Annular fissures are suggested to be associated with low back pain (LBP). Magnetic resonance imaging (MRI) is a sensitive method, yet fissures are sometimes unobservable in T2-weighted MR-images, even though fissure information is present in the image. Image features can mathematically be calculated from MR-images and might reveal fissure characteristics. METHODS: Forty four LBP patients who underwent MRI, low-pressure discography (<50 psi), and computed tomography (CT) sequentially in 1 day, were reviewed. After semi-automated segmentation of 126 discs, image features were extracted from the T2-weighted images. The number of image features was reduced with principle component analysis (PCA). CT-discograms were graded and dichotomized regarding extension and width of fissures. IVDs were divided into fissures extending to outer annulus versus short/no fissures. Fissure width was dichotomized into narrow (<10%) versus broad fissures (>10%), and into moderately broad (10%-50%) versus very broad fissures (>50%). Logistic regression was performed to investigate if image features could depict fissure extension to outer annulus and fissure width. As a sub-analysis, the association between image features used to depict fissure characteristics and discography-provoked pain-response were investigated. RESULTS: Fissure extension could be depicted with sensitivity/specificity = 0.97/0.77 and area under curve (AUC) = 0.97. Corresponding results for width depiction were sensitivity/specificity = 0.94/0.39 and 0.85/0.62, and AUC = 0.86 and 0.81 for narrow versus broad and moderately broad versus very broad fissures respectively. Pain prediction with image features used for depicting fissure characteristics showed sensitivity/specificity = 0.90/0.36, 0.88/0.4, 0.93/0.33; AUC = 0.69, 0.75, and 0.73 respectively. CONCLUSION: Standard MR-images contains fissure information associated to pain that can be depicted with image features, enabling non-invasive phenotyping of potentially painful annular fissures.Level of Evidence: 2.

MRI During Spinal Loading Reveals Intervertebral Disc Behavior Corresponding to Discogram Findings of Annular Fissures and Pain Provocation.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: The aim of this study was to investigate whether spinal loading, depicted with magnetic resonance imaging (MRI), induces regional intervertebral disc (IVD) differences associated with presence and width of annular fissure and induced pain at discography. SUMMARY OF BACKGROUND DATA: Annular fissures play a role in low back pain (LBP) but cannot be accurately characterized with conventional MRI. Recently, annular fissures were suggested to influence different load-induced IVD behavior during MRI when comparing LBP-patients and controls. Thus, the loading effect could characterize behavior related to annular fissures noninvasively with MRI. METHODS: Lumbar spines of 30 LBP-patients were investigated with MRI with and without loading, discography and CT. Five IVD regions were outlined on sagittal MRI images. Difference in normalized signal intensity (SI) with and without loading was calculated for each region. Eighty-three CT-discograms were graded regarding presence and width of fissures. Discograms were classified as pain-positive if a concordant pain response was obtained at a pressure <50 psi. RESULTS: Comparing IVDs with outer fissures with IVDs without fissures, loading induced different behavior in the two ventral regions and in the posterior region. Higher SI increase in the central region was induced in IVDs with narrower fissures compared to IVDs with wider fissures. In the group of pain-negative discograms, a SI decrease was induced in the dorsal region whereas lack of such in the pain-positive group. CONCLUSION: The spinal loading-effect, depicted with MRI, reveals different regional behaviors between IVDs with outer fissures compared to those without, and between IVDs with narrow and broad fissures, as well as within posterior annulus between pain-positive and pain-negative discograms. Findings are of importance for future attempts to uncover phenotypes of painful IVDs. LEVEL OF EVIDENCE: 2.

High immunohistochemical expression of p-AKT predicts inferior survival in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

Chemotherapy and rituximab (R) is current standard therapy in diffuse large B-cell lymphoma (DLBCL), but a substantial proportion of patients still fail to reach sustained remission. In vitro studies have indicated that rituximab resistance could be accompanied by dysregulated apoptotic pathways, such as the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which can be constitutively activated in DLBCL. In this retrospective, immunohistochemical study on 106 patients treated with R-CHO(E)P (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab [+etoposide]), we investigated the prognostic role of proteins involved in different apoptotic pathways; phosphorylated AKT (p-AKT), bcl-2, MCL1, bcl-xL, Bax and Bak. High p-AKT expression (>108 cells/mm2, highest quartile, n=27) predicted worse progression-free (PFS) (P=0.02) and overall (OS) (P=0.01) survival, independent of International Prognostic Index and sex. Also bcl-2+ (cut-off 50%) predicted worse PFS (P=0.005) and OS (P=0.05) but after adjustment for clinical factors only the influence on PFS (P=0.03) remained significant. The prognostic impact of p-AKT overexpression was independent of bcl-2 status. MCL1, bcl-xL, Bax and Bak expression did not add any prognostic information. Our results suggest that high p-AKT expression predicts worse outcome, possibly indicating that inhibition of the activated PI3K/AKT pathway could be of clinical interest in DLBCL patients. In addition, bcl-2 status could have prognostic importance also in the era of immunochemotherapy.