Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial.

OBJECTIVE: To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint. DESIGN: Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Two years after ACI treatment, 93% of patients were KOOS responders having improved by ≥10 points compared with their pre-operative level. The primary endpoint of the study was met and demonstrated that the KOOS response rate is markedly greater than 40% with a lower 95% CI (confidence interval) of 86.1, more than twice the pre-specified no-effect level. KOOS improvement (least squares mean) was 42.0 ± 1.8 points (95% CI between 38.4 and 45.7). Mean changes from baseline were significant in the overall KOOS and in all 5 KOOS subscores from Month 3 (first measurement) to Month 24 (inclusive) (P < 0.0001). The mean MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 24 months reached 80.0 points (95% CI: 70.0-90.0 points) and 92.1 points in lesions ≤ 5 cm2. CONCLUSIONS: Overall, hydrogel-based ACI proved to be a valuable treatment option for patients with large cartilage defects in the knee as demonstrated by early, statistically significant, and clinically meaningful improvement up to 2 years follow-up. Parallel to the clinical improvements, MRI analyses suggested increasing maturation, re-organization, and integration of the repair tissue. TRIAL REGISTRATION: NCT03319797; EudraCT No.: 2016-002817-22.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

OBJECTIVE: To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. DESIGN: Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. RESULTS: No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. CONCLUSIONS: Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm.

Impaired cognitive flexibility represents a widespread symptom in psychiatric disorders, including major depressive disorder (MDD), a disease, characterized by an imbalance of neurotransmitter concentrations. While memory formation is mostly associated with glutamate, also gamma-Aminobutyric acid (GABA) and serotonin show attributions in a complex interplay between neurotransmitter systems. Treatment with selective serotonin reuptake inhibitors (SSRIs) does not solely affect the serotonergic system but shows downstream effects on GABA- and glutamatergic neurotransmission, potentially helping to restore cognitive function via neuroplastic effects. Hence, this study aims to elaborate the effects of associative relearning and SSRI treatment on GABAergic and glutamatergic function within and between five brain regions using magnetic resonance spectroscopy imaging (MRSI). In this study, healthy subjects were randomized into four groups which underwent three weeks of an associative relearning paradigm, with or without emotional connotation, under SSRI (10mg escitalopram) or placebo administration. MRSI measurements, using a spiral-encoded, 3D-GABA-edited MEGA-LASER sequence at 3T, were performed on the first and last day of relearning. Mean GABA+/tCr (GABA+ = GABA + macromolecules; tCr = total creatine) and Glx/tCr (Glx = glutamate + glutamine) ratios were quantified in a ROI-based approach for the hippocampus, insula, putamen, pallidum and thalamus, using LCModel. A total of 66 subjects ((37 female, mean age ± SD = 25.4±4.7) for Glx/tCr and 58 subjects (32 female, mean age ± SD = 25.1±4.7) for GABA+/tCr were included in the final analysis. A significant measurement by region and treatment (SSRI vs placebo) interaction on Glx/tCr ratios was found (pcor=0.017), with post hoc tests confirming differential effects on hippocampus and thalamus (pcor=0.046). Moreover, treatment by time comparison, for each ROI independently, showed a reduction of hippocampal Glx/tCr ratios after SSRI treatment (puncor=0.033). No significant treatment effects on GABA+/tCr ratios or effects of relearning condition on any neurotransmitter ratio could be found. Here, we showed a significant SSRI- and relearning-driven interaction effect of hippocampal and thalamic Glx/tCr levels, suggesting differential behavior based on different serotonin transporter and receptor densities. Moreover, an indication for Glx/tCr adaptions in the hippocampus after three weeks of SSRI treatment could be revealed. Our findings are in line with animal studies reporting glutamate adaptions in the hippocampus following chronic SSRI intake. Due to the complex interplay of serotonin and hippocampal function, involving multiple serotonin receptor subtypes on glutamatergic cells and GABAergic interneurons, the interpretation of underlying neurobiological actions remains challenging.

Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study.

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability. Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed. Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22-69) years with an Expanded Disability Status Score of 2 (0-8) and a disease duration of 11 (5-40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed. Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year. Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

Potential predictive value of axial T2 mapping at 3 Tesla MRI in patients with untreated patellar cartilage defects over a mean follow-up of four years.

OBJECTIVE: The objective was to demonstrate the potential of axial T2 mapping for quantification of untreated early-stage patellar cartilage lesions over time and to assess its capability as a potential predictive marker for future progression. STUDY DESIGN & METHODS: Thirty patients (mean age, 36.7 ± 11.1 years; 16 males), with early-stage patellar cartilage defects (≤ICRS grade 2) at baseline and no treatment during follow up (4.0 ± 1.6 years) were enrolled. Morphological cartilage changes over time were subdivided into a Progression, Non-Progression Group and Regression Group. Quantitative analysis of cartilage defects and healthy reference was performed by means of global and zonal T2 mapping (deep and superficial cartilage T2 values) at both time points. Statistical evaluation included analysis of variance (ANOVA), paired t Test's and ROC analysis. RESULTS: The Progression Group (N = 11) had significantly higher global T2 values at baseline (57.4 ± 7.8 ms) than patients without (N = 17) (40.6 ± 6.9 ms) (P < 0.01). Furthermore the Non-Progression Group showed only a minor increase in global T2 relaxation times to 43.1 ± 7.9 ms (P = 0.07) at follow up, whereas in the progression group global (68,7 ± 19 ms: P = 0.02) and superficial T2 values (65,8 ± 8.2-79.8 ± 24.4 ms; P = 0.03) increased significantly. T2 values for healthy reference cartilage remained stable. In 2 patients an improvement in ICRS grading was observed (Regression Group) with decreasing T2 values. The ROC analysis showed an area under the curve of 0.92 (95%CI 0.82-1.0). At a cut-off value of 47.15 ms, we found a sensitivity of 92% (false-positive rate of 18%) for future progression of cartilage defects. CONCLUSIONS: This study provides evidence regarding the possible potential of axial T2 mapping as a tool for quantification and prediction of patellar cartilage defect progression in untreated defects.

[Biochemical cartilage imaging-update 2019]. / Biochemische Knorpeldiagnostik ­ Update 2019.

BACKGROUND: Cartilage imaging using magnetic resonance imaging (MRI) is increasingly used for early detection of cartilage damage. Biochemical MR methods to assess cartilage damage are essential for optimal treatment planning. PURPOSE: The aim of this review is to provide an update on advanced cartilage imaging based on biochemical MR techniques. The clinical applications and additional benefits compared to conventional MRI are presented. MATERIALS AND METHODS: A literature search of PubMed regarding the clinical applications of various biochemical MR methods and morphological MR imaging was performed. RESULTS: While T2 mapping can be easily implemented on clinical routine MR scanners, the T1rho method is technically more demanding and is not available on all MR scanners. dGEMRIC, which can be performed with all field strengths, is now severely restricted due to the recent decision of the European Medical Agency (EMA) to withdraw linear gadolinium contrast agents from the market because of proven gadolinium deposition in the brain. Sodium imaging is the most sensitive MRI method for glycosaminoglycan (GAG), but is limited to 7 T. In addition to early diagnosis of cartilage degeneration before morphological changes are visible, biochemical MRI offers predictive markers, e.g., effect of lifestyle changes or assessing results of cartilage repair surgery. CONCLUSION: Cartilage imaging based on biochemical MRI allows a shift from qualitative to quantitative MRI. Biochemical MRI plays an increasingly important role in the early diagnosis of cartilage degeneration for monitoring of disease-modifying drugs and as predictive imaging biomarker in clinical diagnostics. In cartilage repair, monitoring of the efficacy of different cartilage repair surgery techniques to develop hyaline-like cartilage can be performed with biochemical MRI.

[Update cartilage imaging of the small joints : Focus on high-field MRI]. / Update Knorpelbildgebung der kleinen Gelenke : Fokus Hochfeld-MRT.

BACKGROUND: Cartilage imaging of small joints is increasingly of interest, as early detection of cartilage damage may be relevant regarding individualized surgical therapies and long-term outcomes. PURPOSE: The aim of this review is to explain modern cartilage imaging of small joints with emphasis on MRI and to discuss the role of methods such as CT arthrography as well as compositional and high-field MRI. MATERIALS AND METHODS: A PubMed literature search was performed for the years 2008-2018. RESULTS: Clinically relevant cartilage imaging to detect chondral damage in small joints remains challenging. Conventional MRI at 3 T can still be considered as a reference for cartilage imaging in clinical routine. In terms of sensitivity, MR arthrography (MR-A) and computed tomography arthrography (CT-A) are superior to non-arthrographic MRI at 1.5 T in the detection of chondral damage. Advanced degenerative changes of the fingers and toes are usually sufficiently characterized by conventional radiography. MRI at field strengths of 3 T and ultrahigh-field imaging at 7 T can provide additional quantifiable, functional and metabolic information. CONCLUSION: Standardized cartilage imaging plays an important role in clinical diagnostics in the ankle joint due to the availability of different and individualized therapeutic concepts. In contrast, cartilage imaging of other small joints as commonly performed in clinical studies has not yet become standard of care in daily clinical routine. Although individual study results are promising, additional studies with large patient collectives are needed to validate these techniques. With rapid development of new treatment concepts radiological diagnostics will play a more significant role in the diagnosis of cartilage lesions of small joints.

A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology.

Introduction The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation. Methods and results A technique was developed that allowed chondrogenic primary (uncultured) cells from bone marrow aspirate concentrate, combined with a composite hydrophilic and fibrillar matrix to be applied arthroscopically to a site of a chondral lesion. The construct was tested in vitro and in animal experiments before clinical trials. Clinical trials involved 60 patients in a prospective study. Symptomatic International Cartilage Repair Society grade 3 and 4a lesions were mapped and treated. Pre- and postoperative clinical assessments showed statistically significant improved outcomes; Lysholm Knee Scoring Scale (mean 52.8 to > 76.4; P < 0.05) International Knee Documentation Committee (mean 39 to > 79 P < 0.05) and Knee injury and Osteoarthritis Outcome Score (64.5 to >89.2 P < 0.05). Postoperative magnetic resonance imaging was evaluated morphologically (magnetic resonance observation of cartilage repair tissue, average MOCART score 72) and qualitatively; the regenerate was comparable to native cartilage. Conclusions This technique is effective, affordable, requires no complex tools and delivers a single-stage treatment that is potentially accessible to any centre capable of performing arthroscopic surgery. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears hyaline like using multiple magnetic resonance measures.

Implementing diffusion-weighted MRI for body imaging in prospective multicentre trials: current considerations and future perspectives.

For body imaging, diffusion-weighted MRI may be used for tumour detection, staging, prognostic information, assessing response and follow-up. Disease detection and staging involve qualitative, subjective assessment of images, whereas for prognosis, progression or response, quantitative evaluation of the apparent diffusion coefficient (ADC) is required. Validation and qualification of ADC in multicentre trials involves examination of i) technical performance to determine biomarker bias and reproducibility and ii) biological performance to interrogate a specific aspect of biology or to forecast outcome. Unfortunately, the variety of acquisition and analysis methodologies employed at different centres make ADC values non-comparable between them. This invalidates implementation in multicentre trials and limits utility of ADC as a biomarker. This article reviews the factors contributing to ADC variability in terms of data acquisition and analysis. Hardware and software considerations are discussed when implementing standardised protocols across multi-vendor platforms together with methods for quality assurance and quality control. Processes of data collection, archiving, curation, analysis, central reading and handling incidental findings are considered in the conduct of multicentre trials. Data protection and good clinical practice are essential prerequisites. Developing international consensus of procedures is critical to successful validation if ADC is to become a useful biomarker in oncology. KEY POINTS: • Standardised acquisition/analysis allows quantification of imaging biomarkers in multicentre trials. • Establishing "precision" of the measurement in the multicentre context is essential. • A repository with traceable data of known provenance promotes further research.

[When is cartilage repair successful?] / Wann ist eine Knorpelreparatur erfolgreich?

Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account.

(2 + 1)D-CAIPIRINHA accelerated MR spectroscopic imaging of the brain at 7T.

PURPOSE: To compare a new parallel imaging (PI) method for multislice proton magnetic resonance spectroscopic imaging (1 H-MRSI), termed (2 + 1)D-CAIPIRINHA, with two standard PI methods: 2D-GRAPPA and 2D-CAIPIRINHA at 7 Tesla (T). METHODS: (2 + 1)D-CAIPIRINHA is a combination of 2D-CAIPIRINHA and slice-CAIPIRINHA. Eight healthy volunteers were measured on a 7T MR scanner using a 32-channel head coil. The best undersampling patterns were estimated for all three PI methods. The artifact powers, g-factors, Cramér-Rao lower bounds (CRLB), and root mean square errors (RMSE) were compared quantitatively among the three PI methods. Metabolic maps and spectra were compared qualitatively. RESULTS: (2 + 1)D-CAIPIRINHA allows acceleration in three spatial dimensions in contrast to 2D-GRAPPA and 2D-CAIPIRINHA. Thus, this sequence significantly decreased the RMSE of the metabolic maps by 12.1 and 6.9%, on average, for 4 < R < 11, compared with 2D-GRAPPA and 2D-CAIPIRINHA, respectively. The artifact power was 22.6 and 8.4% lower, and the CRLB were 3.4 and 0.6% lower, respectively. CONCLUSION: (2 + 1)-CAIPIRINHA can be implemented for multislice MRSI in the brain, enabling higher accelerations than possible with two-dimensional (2D) parallel imaging methods. An eight-fold acceleration was still feasible in vivo with negligible PI artifacts with lipid decontamination, thus decreasing the measurement time from 120 to 15 min for a 64 × 64 × 4 matrix. Magn Reson Med 78:429-440, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

A Review of Numerical Simulation and Analytical Modeling for Medical Devices Safety in MRI.

OBJECTIVES: To review past and present challenges and ongoing trends in numerical simulation for MRI (Magnetic Resonance Imaging) safety evaluation of medical devices. METHODS: A wide literature review on numerical and analytical simulation on simple or complex medical devices in MRI electromagnetic fields shows the evolutions through time and a growing concern for MRI safety over the years. Major issues and achievements are described, as well as current trends and perspectives in this research field. RESULTS: Numerical simulation of medical devices is constantly evolving, supported by calculation methods now well-established. Implants with simple geometry can often be simulated in a computational human model, but one issue remaining today is the experimental validation of these human models. A great concern is to assess RF heating on implants too complex to be traditionally simulated, like pacemaker leads. Thus, ongoing researches focus on alternative hybrids methods, both numerical and experimental, with for example a transfer function method. For the static field and gradient fields, analytical models can be used for dimensioning simple implants shapes, but limited for complex geometries that cannot be studied with simplifying assumptions. CONCLUSIONS: Numerical simulation is an essential tool for MRI safety testing of medical devices. The main issues remain the accuracy of simulations compared to real life and the studies of complex devices; but as the research field is constantly evolving, some promising ideas are now under investigation to take up the challenges.

Suppression of plasma free fatty acids reduces myocardial lipid content and systolic function in type 2 diabetes.

BACKGROUND AND AIM: Type 2 diabetes (T2DM) is closely associated with the development of heart failure, which might be related with impaired substrate metabolism and accumulation of myocardial lipids (MYCL). The aim of this study was to investigate the impact of an acute pharmacological inhibition of adipose tissue lipolysis leading to reduced availability of circulating FFA on MYCL and heart function in T2DM. METHODS AND RESULTS: 8 patients with T2DM (Age: 56 ± 11; BMI: 28 ± 3.5 kg/m(2); HbA1c: 7.29 ± 0.88%) were investigated on two study days in random order. Following administration of Acipimox or Placebo MYCL and heart function were measured by (1)H-magnetic-resonance-spectroscopy and tomography at baseline, at 2 and at 6 h. Acipimox reduced circulating FFA by -69% (p < 0.001), MYCL by -39 ± 41% (p < 0.001) as well as systolic heart function (Ejection Fraction (EF): -13 ± 8%, p = 0.025; Cardiac Index: -16 ± 15%, p = 0.063 compared to baseline). Changes in plasma FFA concentrations strongly correlated with changes in MYCL (r = 0.707; p = 0.002) and EF (r = 0.651; p = 0.006). Diastolic heart function remained unchanged. CONCLUSIONS: Our results indicate, that inhibition of adipose tissue lipolysis is associated with a rapid depletion of MYCL-stores and reduced systolic heart function in T2DM. These changes were comparable to those previously found in insulin sensitive controls. MYCL thus likely serve as a readily available energy source to cope with short-time changes in FFA availability.

Diffusion-weighted imaging of breast tumours at 3 Tesla and 7 Tesla: a comparison.

OBJECTIVES: To compare bilateral diffusion-weighted MR imaging (DWI) at 3 T and 7 T in the same breast tumour patients. METHODS: Twenty-eight patients were included in this IRB-approved study (mean age 56 ± 16 years). Before contrast-enhanced imaging, bilateral DWI with b = 0 and 850 s/mm(2) was performed in 2:56 min (3 T) and 3:48 min (7 T), using readout-segmented echo planar imaging (rs-EPI) with a 1.4 × 1.4 mm(2) (3 T)/0.9 × 0.9 mm(2) (7 T) in-plane resolution. Apparent diffusion coefficients (ADC), signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were assessed. RESULTS: Twenty-eight lesions were detected (18 malignant, 10 benign). CNR and SNR were comparable at both field strengths (p > 0.3). Mean ADC values at 7 T were 4-22% lower than at 3 T (p ≤ 0.03). An ADC threshold of 1.275 × 10(-3) mm(2)/s resulted in a diagnostic specificity of 90% at both field strengths. The sensitivity was 94% and 100% at 3 T and 7 T, respectively. CONCLUSION: 7-T DWI of the breast can be performed with 2.4-fold higher spatial resolution than 3 T, without significant differences in SNR if compared to 3 T. KEY POINTS: • 7 T provides a 2.4-fold higher resolution in breast DWI than 3 T • 7 T DWI has a high diagnostic accuracy comparable to that at 3 T • At 7 T malignant lesions had 22 % lower ADC than at 3 T (p < 0.001).

Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss.

Recently, olfactory training has been introduced as a promising treatment for patients with olfactory dysfunction. However, less is known about the neuronal basis and the influence on functional networks of this training. Thus, we aimed to investigate the neuroplasticity of chemosensory perception through an olfactory training program in patients with smell loss. The experimental setup included functional MRI (fMRI) experiments with three different types of chemosensory stimuli. Ten anosmic patients (7f, 3m) and 14 healthy controls (7f, 7m) underwent the same testing sessions. After a 12-week olfactory training period, seven patients (4f, 3m) were invited for follow-up testing using the same fMRI protocol. Functional networks were identified using independent component analysis and were further examined in detail using functional connectivity analysis. We found that anosmic patients and healthy controls initially use the same three networks to process chemosensory input: the olfactory; the somatosensory; and the integrative network. Those networks did not differ between the two groups in their spatial extent, but in their functional connectivity. After the olfactory training, the sensitivity to detect odors significantly increased in the anosmic group, which was also manifested in modifications of functional connections in all three investigated networks. The results of this study indicate that an olfactory training program can reorganize functional networks, although, initially, no differences in the spatial distribution of neural activation were observed.

Effects of chronic peripheral olfactory loss on functional brain networks.

The effects of sensory loss on central processing in various sensory systems have already been described. The olfactory system holds the special ability to be activated by a sensorimotor act, without the presentation of an odor. In this study, we investigated brain changes related to chronic peripheral smell loss. We included 11 anosmic patients (eight female, three male; mean age, 43.5 years) with smell loss after an infection of the upper respiratory tract (mean disease duration, 4.64 years) and 14 healthy controls (seven female, seven male; mean age, 30.1 years) in a functional magnetic resonance imaging experiment with a sniffing paradigm. Data were analyzed using group-independent component analysis and functional connectivity analysis. Our results revealed a spatially intact olfactory network in patients, whereas major aberrations due to peripheral loss were observed in functional connectivity through a variety of distributed brain areas. This is the first study to show the re-organization caused by the lack of peripheral input. The results of this study indicate that anosmic patients hold the ability to activate an olfaction-related functional network through the sensorimotor component of odor-perception (sniffing). The areas involved were not different from those that emerged in healthy controls. However, functional connectivity appears to be different between the two groups, with a decrease in functional connectivity in the brain in patients with chronic peripheral sensory loss. We can further conclude that the loss of the sense of smell may induce far-reaching effects in the whole brain, which lead to compensatory mechanisms from other sensory systems due to the close interconnectivity of the olfactory system with other functional networks.

Morphological and compositional monitoring of a new cell-free cartilage repair hydrogel technology - GelrinC by MR using semi-quantitative MOCART scoring and quantitative T2 index and new zonal T2 index calculation.

OBJECTIVE: To evaluate cartilage repair tissue (RT) using MOCART scoring for morphological and T2 mapping for biochemical assessment following implantation of GelrinC, a biosynthetic, biodegradable hydrogel implant. DESIGN: MR imaging (1.5/3T) was performed on 21 patients at six sites. Standard protocols were used for MOCART evaluation at 1 week (baseline) 1, 3, 6, 12, 18 and 24 months. Multi-echo SE was used for T2 mapping. Global (T2 in RT divided by T2 in normal cartilage) and zonal T2 index (deep T2 divided by superficial T2) of RT were calculated. RESULTS: Average MOCART score was 71.8 (95% CI 62.2 to 81.3) at six, 75.2 (95% CI 62.8 to 87.5) at twelve, 71.8 (95% CI 55.4 to 88.2) at eighteen and 84.4 (95% CI 77.7 to 91.0) at twenty-four months. The global T2 index ranged between 0.8 and 1.2 (normal healthy cartilage) in 1/11 (9%) patients at baseline, 8/12 (67%) at 12 months, 11/13 (85%) at 18 months and 13/16 (81%) at 24 months. The zonal T2 index for RT was <20% difference to the zonal T2 index for normal cartilage in: 6/12 patients (50%) at 12 months, 7/13 (53.8%) at 18 months and 10/16 (63.5%) at 24 months. The standard deviation for T2 showed a significant decrease over the study. CONCLUSIONS: The increase of MOCART scores over follow-up indicates improving cartilage repair tissue. Global and zonal T2 repair values at 24 months reached normal cartilage in 81% and 63.5% of the patients respectively, reflecting collagen organization similar to hyaline cartilage.

[Physical interactions in MRI: Some rules of thumb for their reduction]. / Physikalische Wechselwirkungen in der MRT : Einige Daumenregeln zu ihrer Reduktion.

Magnetic resonance imaging (MRI) is one of the most powerful and at the same time gentlest clinical imaging techniques at the present time; however, the enormous physical complexity as well as simple inattentiveness (projectile effect) implicate a significant risk potential and place high demands on the MR operator to ensure a safe workflow. A sound knowledge of the potential MR interactions is the foundation for a safe and profitable operation for all parties.The first part of this article deals with the three most important sources of physical interaction, i.e. static magnetic field, gradient and high-frequency (HF) fields. The paper discusses the differences between each type of field with respect to the impact on human beings, the interactions with magnetic and electrically conducting objects/implants and the relevant safety standards. Each section is followed by simple rules of thumb to minimize potentially unwanted physical MRI interactions.