Marta Tibiletti

Advances in the diagnosis of degenerated lumbar discs and their possible clinical application

PurposeOne possible source of chronic low back pain is a degenerated intervertebral disc. In this review, various diagnostic methods for the assessment of the presence of degenerative changes are described. These include clinical MRI, a number of novel MRI techniques and nuclear magnetic resonance spectroscopy.MethodsNon-systematic literature review.ResultsClinical MRI is the most commonly employed technique to determine the general “health status” of the intervertebral disc. Novel MRI techniques, such as quantitative MRI, T1ρ MRI, sodium MRI and nuclear magnetic resonance spectroscopy, are more sensitive in quantifying the biochemical changes of disc degeneration, as measured by alteration in collagen structure, as well as water and proteoglycan loss. As potential future diagnostic alternatives, miniature sensors are currently being developed to measure parameters associated with the disc degeneration cascade, such as intradiscal pressure and PG concentration. However, none of the methods listed above show sufficient specificity to identify a degenerated disc as the actual source of the pain. Provocative discography is the only test aimed at a direct diagnosis of discogenic pain, but it has a high false positive rate and there is some evidence of long-term adverse effects. Imaging techniques have also been tested for this purpose, but their validity has not been confirmed and they do appear to be problematic.ConclusionsA reliable diagnostic tool that could help a clinician to determine if a disc is the source of the pain in patients with chronic LBP is still not available. New MRI techniques are under investigation that could result in a significant improvement over current methods, particularly as they can allow monitoring, not only of morphological but also of biochemical changes.

Multistage three-dimensional UTE lung imaging by image-based self-gating

To combine image‐based self‐gating (img‐SG) with ultrashort echo time (UTE) three‐dimensional (3D) acquisition for multistage lung imaging during free breathing.

Three-dimensional accurate detection of lung emphysema in rats using ultra-short and zero echo time MRI.

Emphysema is a life‐threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non‐invasive pre‐clinical and clinical detection and longitudinal follow‐up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three‐dimensional (3D) zero echo time (ZTE) and 3D ultra‐short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro‐computed tomography images were acquired 4 weeks after the PPE challenge. Signal‐to‐noise ratios (SNRs) were measured in PPE‐treated and control rats. T2* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE‐treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T2* values in PPE‐challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE‐treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE‐treated and non‐PPE‐treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non‐invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation exposure typical of micro‐computed tomography. Copyright

Disc cell therapies: critical issues

BackgroundDisc cell therapies, in which cells are injected into the degenerate disc in order to regenerate the matrix and restore function, appear to be an attractive, minimally invasive method of treatment. Interest in this area has stimulated research into disc cell biology in particular. However, other important issues, some of which are discussed here, need to be considered if cell-based therapies are to be brought to the clinic.PurposeFirstly, a question which is barely addressed in the literature, is how to identify patients with ‘degenerative disc disease’ who would benefit from cell therapy. Pain not disc degeneration is the symptom which drives patients to the clinic. Even though there are associations between back pain and disc degeneration, many people with even severely degenerate discs, with herniated discs or with spinal stenosis, are pain-free. It is not possible using currently available techniques to identify whether disc repair or regeneration would remove symptoms or prevent symptoms from occurring in future. Moreover, the repair process in human discs is very slow (years) because of the low cell density which can be supported nutritionally even in healthy human discs. If repair is necessary for relief of symptoms, questions regarding quality of life and rehabilitation during this long process need consideration.Also, some serious technical issues remain. Finding appropriate cell sources and scaffolds have received most attention, but these are not the only issues determining the feasibility of the procedure. There are questions regarding the safety of implanting cells by injection through the annulus whether the nutrient supply to the disc is sufficient to support implanted cells and whether, if cells are able to survive, conditions in a degenerate human disc will allow them to repair the damaged tissue.ConclusionsIf cell therapy for treatment of disc-related disorders is to enter the clinic as a routine treatment, investigations must examine the questions related to patient selection and the feasibility of achieving the desired repair in an acceptable time frame. Few diagnostic tests that examine whether cell therapies are likely to succeed are available at present, but definite exclusion criteria would be evidence of major disc fissures, or disturbance of nutrient pathways as measured by post-contrast MRI.

Is the Transport of a Gadolinium-Based Contrast Agent Decreased in a Degenerated or Aged Disc? A Post Contrast MRI Study

A post contrast magnetic resonance imaging study has been performed in a wide population of low back pain patients to investigate which radiological and phenotypic characteristics influence the penetration of the contrast agent in lumbar discs in vivo. 37 patients affected by different pathologies (disc herniation, spondylolisthesis, foraminal stenosis, central canal stenosis) were enrolled in the study. The selected population included 26 male and 11 female subjects, with a mean age of 42.4±9.3 years (range 18–60). Magnetic resonance images of the lumbar spine were obtained with a 1.5 T scanner (Avanto, Siemens, Erlangen, Germany) with a phased-array back coil. A paramagnetic non–ionic contrast agent was injected with a dose of 0.4 ml/kg. T1-weighted magnetic resonance images were subsequently acquired at 5 time points, 5 and 10 minutes, 2, 4 and 6 hours after injection. Endplates presented clear enhancement already 5 minutes after injection, and showed an increase in the next 2 hours followed by a decrease. At 5 and 10 minutes, virtually no contrast medium was present inside the intervertebral disc; afterwards, enhancement significantly increased. Highly degenerated discs showed higher enhancement in comparison with low and medium degenerated discs. Discs classified as Pfirrmann 5 showed a statistically significant higher enhancement than Pfirrmann 1, 2 and 3 at all time points but the first one, possibly due to vascularization. Disc height collapse and Modic changes significantly increased enhancement. Presence of endplate defects did not show any significant influence on post contrast enhancement, but the lack of a clear classification of endplate defects as seen on magnetic resonance scans may be shadowing some effects. In conclusion, disc height, high level of degeneration and presence of Modic changes are factors which increase post contrast enhancement in the intervertebral disc. The effect of age could not be demonstrated.

An array of fully-integrated quadrature TX/RX NMR field probes for MRI trajectory mapping

In this paper we present fully-integrated field probes for real-time trajectory mapping during magnetic resonance imaging (MRI) experiments. The field probes co-integrate an NMR microcoil and the required transceiver electronics on a single ASIC manufactured in a 0.13μm CMOS technology. Thanks to an on-chip PLL, power amplifier and low-IF quadrature receiver, all connections to and from the chip carry only low frequency signals allowing for an effective reduction of the magnetic coupling between the field probes and the MRI scanner during imaging. The small form factor and low power consumption of 16.5mW allows for the realization of arrays of field probes, which in contrast to single probes enable the correction of higher order field imperfections. Measured trajectory maps acquired with a prototype array consisting of four probes demonstrate the excellent sensor performance achievable using the proposed approach.

Multistage self-gated lung imaging in small rodents

To investigate the exploitation of the self‐gating signal in ultrashort echo time (UTE) two‐dimensional (2D) acquisitions of freely breathing rats to reconstruct multiple respiratory stages.

Respiratory self-gated 3D UTE for lung imaging in small animal MRI.

To investigate retrospective respiratory gating of three‐dimensional ultrashort echo time (3D UTE) lung acquisition in free‐breathing rats using k‐space center self gating signal (DC‐SG) and 3D image‐based SG (3D‐Img‐SG).

Pulmonary perfusion quantification with flow-sensitive inversion recovery (FAIR) UTE MRI in small animal imaging

Blood perfusion in lung parenchyma is an important property for assessing lung function. In small animals, its quantitation is limited even with radioactive isotopes or dynamic contrast‐enhanced MRI techniques. In this study, the feasibility flow‐sensitive alternating inversion recovery (FAIR) for the quantification of blood flow in lung parenchyma in free breathing rats at 7 T has been investigated. In order to obtain sufficient signal from the short T2* lung parenchyma, a 2D ultra‐short echo time (UTE) Look‐Locker read‐out has been implemented. Acquisitions were segmented to maintain acquisition time within an acceptable range. A method to perform retrospective respiratory gating (DC‐SG) has been applied to investigate the impact of respiratory movement. Reproducibilities within and between sessions were estimated, and the ability of FAIR‐UTE to identify the decrease of lung perfusion under hyperoxic conditions was tested. The implemented technique allowed for the visualization of lung parenchyma with excellent SNR and no respiratory artifact even in ungated acquisitions. Lung parenchyma perfusion was obtained as 32.54 ± 2.26 mL/g/min in the left lung, and 34.09 ± 2.75 mL/g/min in the right lung. Application of retrospective gating significantly but minimally changes the perfusion values, implying that respiratory gating may not be necessary with this center‐our acquisition method. A decrease of 10% in lung perfusion was found between normoxic and hyperoxic conditions, proving the feasibility of the FAIR‐UTE approach to quantify lung perfusion changes.

Functional Proton MRI in Emphysematous Rats.

ObjectiveTo demonstrate the feasibility of proton magnetic resonance imaging (MRI) ventilation–related maps in rodents for the evaluation of lung function in the presence of pancreatic porcine elastase (PPE)-induced emphysema. Materials and MethodsTwelve rats were equally divided into 3 groups: group 1 (no administration of PPE); group 2 (PPE selectively only in the left lung); and group 3 (PPE administered in both lungs). Magnetic resonance imaging (MRI) and computed tomographic (CT) data were acquired at baseline, at 2 weeks and 4 weeks after administration, after which the animals were euthanized. The MRI protocol comprised a golden angle 2-dimensional ultrashort echo time MRI sequence [echo time, 0.343 millisecond (ms); repetition time, 120 ms; 12 slides with thickness, 1 mm; acquisition time, 30 minutes], from which inspiration and expiration images were reconstructed after the extraction of a self-gating signal. Inspiration images were registered to images at expiration, and expansion maps were created by calculating the specific difference in signal intensity. The lungs were segmented, and the mean specific expansion (MSE) calculated as an established surrogate for fractional ventilation. Computed tomographic data provided lung density (peak of the Hounsfield unit histogram, HU_P), whereas histology provided the mean linear intercept for each lung. ResultsTwo weeks after administration, the control group had a mean MSE in both lungs corresponding to 96% of the baseline. Group 2 had 85% of the baseline, and group 3 had 57%. Considering the PPE-treated lungs alone, a significant reduction in MSE of 27% at 2 weeks and 40% at 4 weeks was found with respect to nontreated lungs. Significant correlations between HU_P and MSE were found at all time points (baseline: r = 0.606, P = 0.0017; 2 weeks: r = 0.837, P ⩽ 0.0001; 4 weeks: r = 0.765, P < 0.0001; all time points: r = 0.739, P < 0.0001). Mean linear intercept values significantly correlated both with MRI MSE (r = −0.770, P < 0.0001) and with CT HU_P (r = −0.882, P < 0.0001). DiscussionThe calculated ventilation-related maps showed a reduction of function in the PPE-treated lungs, both compared to the nontreated lungs and to the baseline values. Moreover, a good agreement between MRI-measured MSE, CT, and histology data quantitatively supports the presence of ventilation deficit in emphysematous lungs.In this work, we have demonstrated the feasibility of ventilation-related maps from non–contrast-enhanced 1H lung MRI, which were capable of tracking changes in lung function over time in emphysematous rats.