Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies.

Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.

PURPOSE: To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. METHODS: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. RESULTS: Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. CONCLUSION: Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.

Imaging human lung perfusion with contrast media: A meta-analysis.

PURPOSE: To pool and summarise published data of pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) of the human lung, obtained with perfusion MRI or CT to provide reliable reference values of healthy lung tissue. In addition, the available data regarding diseased lung was investigated. METHODS: PubMed was systematically searched to identify studies that quantified PBF/PBV/MTT in the human lung by injection of contrast agent, imaged by MRI or CT. Only data analysed by 'indicator dilution theory' were considered numerically. Weighted mean (wM), weighted standard deviation (wSD) and weighted coefficient of variance (wCoV) were obtained for healthy volunteers (HV), weighted according to the size of the datasets. Signal to concentration conversion method, breath holding method and presence of 'pre-bolus' were noted. RESULTS: PBV was obtained from 313 measurements from 14 publications (wM: 13.97 ml/100 ml, wSD: 4.21 ml/100 ml, wCoV 0.30). MTT was obtained from 188 measurements from 10 publications (wM: 5.91 s, wSD: 1.84 s wCoV 0.31). PBF was obtained from 349 measurements from 14 publications (wM: 246.26 ml/100 ml ml/min, wSD: 93.13 ml/100 ml ml/min, wCoV 0.38). PBV and PBF were higher when the signal was normalised than when it was not. No significant differences were found for PBV and PBF between breathing states or between pre-bolus and no pre-bolus. Data for diseased lung were insufficient for meta-analysis. CONCLUSION: Reference values for PBF, MTT and PBV were obtained in HV. The literature data are insufficient to draw strong conclusions regarding disease reference values.

Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI.

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

Semi-quantitative evaluation of signal intensity and contrast-enhancement in Modic changes.

BACKGROUND: Semi-quantitative evaluation of Modic changes (MCs) has recently been proposed as a way to standardise and increase repeatability of clinical studies. This study is aimed at developing semi-quantitative measures of enhancement, given by contrast agent injection, on T1-weighted images in MCs, and to investigate their reliability and relation with MC types. METHODS: Thirty-seven subjects suffering from low back pain underwent T1-weighted and T2-weighted turbo spin-echo sequences. Five minutes after the injection of a paramagnetic contrast agent, a second T1-weighted sequence was acquired. Regions of interest (ROIs) corresponding to MCs were selected manually on the unenhanced image; control ROIs in the "healthy" bone marrow were selected. For each ROI, the mean signal intensity (SI) of unenhanced pixels and the mean absolute and normalised difference in SI between unenhanced and contrast-enhanced pixels values were calculated. RESULTS: A total of 103 MCs were recognised and 61 were semi-quantitatively analysed: 16 type I, 34 type II and 11 type I/II. Regarding controls, MCs I showed a lower SI on the unenhanced T1-weighted images and a marked contrast enhancement (CE); MCs II showed a higher SI than controls on unenhanced images and a lower or comparable CE; and MCs I/II presented an intermediate SI on the unenhanced images and a marked CE. Inter-rater and intra-rater agreements were found to be excellent or substantial. CONCLUSIONS: Semi-quantitative measurements could differentiate MC types in terms of unenhanced SI and of CE with respect to "healthy" bone marrow.

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

PURPOSE: 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). METHODS: Seven rats were investigated with a quasi-random 3D UTE protocol. Low-resolution time-resolved sliding-window images were reconstructed with a 3D golden-angle radial sparse parallel (GRASP) reconstruction to extract a 3D-Img-SG signal, whereas DC-SG was extracted from the center of k-space. Both signals were sorted into 10 respiratory bins. Signal-to-noise ratio (SNR) and normalized signal intensity (NSI) in lung parenchyma, image sharpness, and lung volume changes were studied in the resulting images to show feasibility of the method. An algorithm for bulk movement identification and removal was implemented. RESULTS: Three-dimensional Img-SG allows reconstruction of different respiratory stages in all acquired datasets, showing clear differences in diaphragm position and significantly different lung volumes, SNR, and NSI in lung parenchyma. Improved sharpness in expiration images was observed compared to ungated images. DC-SG did not result in clear different diaphragm position in all cases. Bulk motion removal improved final image sharpness. CONCLUSION: Low-resolution 3D GRASP reconstruction allowed for extraction of an effective gating signal for 3D-Img-SG. The DC-SG method did not work in cases for which respiratory frequencies were inconsistent. Magn Reson Med 78:739-745, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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.

Multistage self-gated lung imaging in small rodents.

PURPOSE: 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. METHODS: Twelve rats were investigated with a 2D golden angle UTE protocol (12 coronal slices, echo time 0.343 ms, repetition time 120 ms, thickness 1 mm, flip angle 30°, matrix 256 × 256, 20-fold oversampling). The self-gating signal was extracted from the k-space center and sorted into five respiration bins (expiration, inspiration, three intermediate stages). Lung volume, sharpness, signal to noise ratio (SNR) and normalized signal intensity (NSI) were investigated. Time resolved images were reconstructed to visualize global animal motion. RESULTS: The method delineated that the lung volume decreased gradually from inspiration to expiration. Sharpness index resulted higher in expiration than in the ungated images. SNR was higher in ungated images and in expiration, decreasing gradually toward inspiration. NSI values presented a similar trend, with ungated images showing lower values than the expiration images. In one animal clear global motion and in seven animals minor movements were identified. CONCLUSION: The presented respiratory gating method allows the reconstruction of different respiratory positions. Improved sharpness in expiration images was observed compared with ungated images. SNR and NSI changes in parenchyma reflect the expected variation of lung tissue density during respiration. Magn Reson Med 75:2448-2454, 2016. © 2015 Wiley Periodicals, Inc.

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

PURPOSE: To combine image-based self-gating (img-SG) with ultrashort echo time (UTE) three-dimensional (3D) acquisition for multistage lung imaging during free breathing. METHODS: Three k-space ordering schemes (modified spiral pattern, quasirandom numbers and multidimensional Golden Angle) providing uniform coverage of k-space were investigated for providing low-resolution sliding-window images for image-based respiratory self-gating. The performance of the proposed techniques were compared with the conventional spiral pattern and standard DC-based self-gated methods in volunteers during free breathing. RESULTS: Navigator-like respiratory signals were successfully extracted from the sliding-window data by monitoring the lung-liver interface displacement. A temporal resolution of 588 ms was adequate to retrieve gating signals from the lung-liver interface. Images reconstructed with the img-SG technique showed significantly better sharpness and apparent diaphragm excursion than any of the DC-SG methods. Direct comparison of the three implemented ordering schemes did not demonstrate any clear superiority of one with respect to the others. CONCLUSION: Image-based respiratory self gating in UTE 3D lung images allows successful retrospective respiratory gating, also enabling reconstruction of intermediate respiratory stages.

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.

Functional Proton MRI in Emphysematous Rats.

OBJECTIVE: To 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 METHODS: Twelve 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. RESULTS: Two 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). DISCUSSION: The 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 H lung MRI, which were capable of tracking changes in lung function over time in emphysematous rats.

Inverse numerical prediction of the transport properties of vertebral endplates in low back pain patients.

A numerical method based on contrast-enhanced MRI to predict the transport properties of spinal structures is presented and used for a population of 32 low back pain patients. Sixty-eight one-dimensional finite element models aimed to replicate the transport of Gd-HP-DO3A were developed, one for each intervertebral disc was investigated. Each model had the same disc height as that measured on the MRI images of specific patients. Transport properties of the vertebral structures were inversely calculated in order to minimize the error between the predicted Gd-HP-DO3A concentration and those determined by MRI acquisitions for specific patients 6 h after a contrast agent injection. Within some limits numerical predictions were generally representative of the Gd-HP-DO3A concentration behavior estimated by contrast-enhanced MRIs. The predicted properties showed high variability within the population. Transport properties were markedly higher than the bulk diffusion coefficients of the nutrients. No significant differences (p=0.31) were observed between the caudal and the cranial endplate zones. Discs had higher transport properties than endplate zones (p<0.001). Comparisons among different age groups revealed no significant differences of the transport properties with aging. The discrepancies between the predictions and the bulk diffusion coefficients of nutrients and Gd-HP-DO3A in water highlighted the complexities of quantifying transport across the EPZs and intervertebral disc.

Disc cell therapies: critical issues.

BACKGROUND: Disc 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. PURPOSE: Firstly, 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. CONCLUSIONS: If 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.

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

PURPOSE: One 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. METHODS: Non-systematic literature review. RESULTS: Clinical 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. CONCLUSIONS: A 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.

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 EMG-controlled neuroprosthesis for daily upper limb support: a preliminary study.

MUNDUS is an assistive platform for recovering direct interaction capability of severely impaired people based on upper limb motor functions. Its main concept is to exploit any residual control of the end-user, thus being suitable for long term utilization in daily activities. MUNDUS integrates multimodal information (EMG, eye tracking, brain computer interface) to control different actuators, such as a passive exoskeleton for weight relief, a neuroprosthesis for arm motion and small motors for grasping. Within this project, the present work integreted a commercial passive exoskeleton with an EMG-controlled neuroprosthesis for supporting hand-to-mouth movements. Being the stimulated muscle the same from which the EMG was measured, first it was necessary to develop an appropriate digital filter to separate the volitional EMG and the stimulation response. Then, a control method aimed at exploiting as much as possible the residual motor control of the end-user was designed. The controller provided a stimulation intensity proportional to the volitional EMG. An experimental protocol was defined to validate the filter and the controller operation on one healthy volunteer. The subject was asked to perform a sequence of hand-to-mouth movements holding different loads. The movements were supported by both the exoskeleton and the neuroprosthesis. The filter was able to detect an increase of the volitional EMG as the weight held by the subject increased. Thus, a higher stimulation intensity was provided in order to support a more intense exercise. The study demonstrated the feasibility of an EMG-controlled neuroprosthesis for daily upper limb support on healthy subjects, providing a first step forward towards the development of the final MUNDUS platform.