A novel magnetic resonance imaging postprocessing technique for the assessment of intervertebral disc degeneration-Correlation with histological grading in a rabbit disc degeneration model.

Introduction:Estimation of intervertebral disc degeneration on magnetic resonance imaging (MRI) is challenging. Qualitative schemes used in clinical practice correlate poorly with pain and quantitative techniques have not entered widespread clinical use. Methods:As part of a prior study, 25 New Zealand white rabbits underwent annular puncture to induce disc degeneration in 50 noncontiguous lumbar discs. At 16 weeks, the animals underwent multi-echo T2 MRI scanning and were euthanized. The discs were stained and examined histologically. Quantitative T2 relaxation maps were prepared using the nonlinear least squares method. Decay Variance maps were created using a novel technique of aggregating the deviation in the intensity of each echo signal from the expected intensity based on the previous rate of decay. Results:Decay Variance maps showed a clear and well demarcated nucleus pulposus with a consistent rate of decay (low Decay Variance) in healthy discs that showed progressively more variable decay (higher Decay Variance) with increasing degeneration. Decay Variance maps required significantly less time to generate (1.0 ± 0.0 second) compared with traditional T2 relaxometry maps (5 (±0.9) to 1788.9 (±116) seconds). Histology scores correlated strongly with Decay Variance scores (r = 0.82, P < .01) and weakly with T2 signal intensity (r = 0.32, P < .01) and quantitative T2 relaxometry (r = 0.39, P < .01). Decay Variance had superior sensitivity and specificity for the detection of degenerate discs when compared to T2 signal intensity or Quantitative T2 mapping. Conclusion:Our results show that using a multi-echo T2 MRI sequence, Decay Variance can quantitatively assess disc degeneration more accurately and with less image-processing time than quantitative T2 relaxometry in a rabbit disc puncture model. The technique is a viable candidate for quantitative assessment of disc degeneration on MRI scans. Further validation on human subjects is needed

Poly[1,4-bis­(ammonio­meth­yl)cyclo­hexane [di-μ-iodido-diiodido­plumbate(II)]]

The title compound, {(C8H20N2)[PbI4]}n, is an inorganic–organic hybrid. The structure is composed of alternate layers of two-dimensional corner-sharing PbI6 octa­hedra ( symmetry) and 1,4-bis­(ammonio­meth­yl)cyclo­hexane cations ( symmetry) extending parallel to the bc plane. The cations inter­act with the inorganic layer via N—H⋯I hydrogen bonding in the right-angled halogen sub-type of the terminal halide hydrogen-bonding motif

Poly[1,4-bis­(ammonio­meth­yl)cyclo­hexane [di-μ-bromido-dibromido­plumbate(II)]]

The title compound, {(C8H20N2)[PbBr4]}n, crystallizes as an inorganic–organic hybrid with alternating layers of diammonium cations and two-dimensional corner-sharing PbBr6 octa­hedra extending parallel to the bc plane, which are eclipsed relative to one another. Both PbBr6 octa­hedra and the organic cation exhibit symmetry. The cations inter­act via N—H⋯Br hydrogen bonding in the right-angled halogen sub-type of the terminal halide hydrogen-bonding motif

4-(8-Eth­oxy-2,3-dihydro-1H-cyclo­penta­[c]quinolin-4-yl)butane-1-peroxol

In the title mol­ecule, C18H23NO3, the hydro­per­oxy­butyl substituent is nearly fully extended, with the four torsion angles in the range 170.23 (10)–178.71 (9)°. The O—O distance in the hydro­peroxide group is 1.4690 (13) Å. This group acts as an inter­molecular hydrogen-bond donor to a quinoline N atom. This results in dimeric units about the respective inversion centers, with graph-set notation R 2 2(18)

X-ray absorption spectroscopy systematics at the tungsten L-edge

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, has been interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W<sup>0</sup>(PMe<sub>3</sub>)<sub>6</sub>], [W<sup>II</sup>Cl<sub>2</sub>(PMePh<sub>2</sub>)<sub>4</sub>], [W<sup>III</sup>Cl<sub>2</sub>(dppe)<sub>2</sub>][PF<sub>6</sub>] (dppe = 1,2-bis(diphenylphosphino)ethane), [W<sup>IV</sup>Cl<sub>4</sub>(PMePh<sub>2</sub>)<sub>2</sub>], [W<sup>V</sup>(NPh)Cl<sub>3</sub>(PMe<sub>3</sub>)<sub>2</sub>], and [W<sup>VI</sup>Cl<sub>6</sub>] correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio (EBR) of the L<sub>3,2</sub>-edges and the L<sub>1</sub> rising-edge energy with metal Z<sub>eff</sub>, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>] and [W<sup>IV</sup>(mdt)<sub>2</sub>(CN)<sub>2</sub>]<sup>2–</sup> (mdt<sup>2–</sup> = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W<sup>IV</sup> species. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: 1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Z<sub>eff</sub> in the species of interest; 2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS; 3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Z<sub>eff</sub> or, as in the case of [W<sup>IV</sup>(mdt)<sub>2</sub>(CO)<sub>2</sub>], add other subtlety by modulating the redox level of other ligands in the coordination sphere

The CCP4 suite : integrative software for macromolecular crystallography

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world

Decay Variance: A novel technique for the diagnosis of intervertebral disc degeneration

Low back pain is the largest cause of disease burden due to morbidity in the world. Despite high burden and prevalence of low back pain, in the majority of cases no specific pathoanatomical causeetween consecutive leve of the pain can be identified. Sufferers without a defined cause are said to suffer from non-specific low back pain (NSLBP). Many putative causes of such back pain have been advanced, with many supposedly culpable structures, but none so strongly as the intervertebral disc. The intervertebral disc is a connective tissue structure between consecutive levels of vertebral bone in the spine of humans, with a proteoglycan rich central nucleus which draws in water and creates a cushion effect between the bones. This normal physiology can become distrupted with loss of these proteoglycans and dessication of the disc, a process referred to as degeneration. Where this degeneration is accompanied by back pain this is referred to as degenerative disc disease. While this is a well defined process histologically, in clinical practice existing radiological techniques for the diagnosis of disc disease do not correlate strongly with patient symptoms and level of back pain. In this thesis I: Briefly review the literature connecting disc degeneration with low back pain with a focus on radiological diagnosis Describe a novel technique for processing MRI images to quantify the irregularity of relaxation across 3 or more time points in a shifting echo-triplet reference frame Describe a set of computer simulations examining the expected performance of this technique at biologically relevant T2 relaxation times, with expected signal to noise ratios at 3T. Describe an animal experiment in which this new processing technique correlates more strongly with the histological severity of degeneration than common existing techniques (Pfirrmann grading onT2WI and quantitative T2 mapping), with fewer false positives in healthy discs. Describe a human study in which this new technique correlates moderately strongly with severity of self reported pain in a cohort of chronic low back pain sufferers Discuss why the findings above are not sufficient to establish a clinical utility for the technique and what further work will need to be undertaken to establish if there is a useful role for this technique in practice

Clinical and Research MRI Techniques for Assessing Spinal Cord Integrity in Degenerative Cervical Myelopathy—A Scoping Review

Background: Degenerative cervical myelopathy (DCM) manifests as the primary cause of spinal cord dysfunction and is non-traumatic, chronic and progressive in nature. Decompressive surgery is typically utilised to halt further disability and neurological dysfunction. The limitations of current diagnostic options surrounding assessment and prognostic potential render DCM still largely a clinical diagnosis. Aims: To outline the limitations of current diagnostic techniques, present evidence behind novel quantitative MRI (qMRI) techniques for assessing spinal cord integrity in DCM and suggest future directions. Method: Articles published up to November 2021 were retrieved from Medline, EMBASE and EBM using key search terms: spinal cord, spine, neck, MRI, magnetic resonance imaging, qMRI, T1, T2, T2*, R2*, DTI, diffusion tensor imaging, MT, magnetisation transfer, SWI, susceptibility weighted imaging, BOLD, blood oxygen level dependent, fMRI, functional magnetic resonance imaging, functional MRI, MRS, magnetic resonance spectroscopy. Results: A total of 2057 articles were retrieved with 68 articles included for analysis. The search yielded 2 articles on Quantitative T1 mapping which suggested higher T1 values in spinal cord of moderate-severe DCM; 43 articles on DTI which indicated a strong correlation of fractional anisotropy and modified Japanese Orthopaedic Association scores; 15 articles on fMRI (BOLD) which demonstrated positive correlation of functional connectivity and volume of activation of various connections in the brain with post-surgical recovery; 6 articles on MRS which suggested that Choline/N-acetylaspartate (Cho/NAA) ratio presents the best correlation with DCM severity; and 4 articles on MT which revealed a preliminary negative correlation of magnetisation transfer ratio with DCM severity. Notably, most studies were of low sample size with short timeframes within 6 months. Conclusions: Further longitudinal studies with higher sample sizes and longer time horizons are necessary to determine the full prognostic capacity of qMRI in DCM