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We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the algebraic description of the magnetization during the transient response—including intrinsic magnetic resonance parameters such as longitudinal and transverse relaxation times (T 1 , T 2 ) and proton density (PD) and experimental conditions such as radiofrequency field (B 1 ) and constant/homogeneous magnetic field (B 0 ) from associated scanners. We exploit the correspondence among three different elements: the signal evolution as a result of a repetitive sequence of blocks of radiofrequency excitation pulses and encoding gradients, the continuous Bloch equations and the mathematical description of a sequence as a linear system. This approach simultaneously provides, in a single measurement, all quantitative parameters of interest as well as associated system imperfections. Finally, we demonstrate the in-vivo applicability of the new concept on a clinical MRI scanner.

The quality of carotid wall MRI can benefit substantially from a dedicated RF coil that is tailored towards the human neck geometry and optimized for image signal-to-noise ratio (SNR), parallel imaging performance and RF penetration depth and coverage. In last decades, several of such dedicated carotid coils were introduced. However, a comparison of the more successful designs is still lacking. To perform a head-to-head comparison over four dedicated MR carotid surface coils with 4, 6, 8 and 30 coil elements, respectively. Ten volunteers were scanned on a 3T scanner. For each subject, multiple black-blood carotid vessel wall images were measured using the four coils with different parallel imaging settings. The performance of the coils was evaluated and compared in terms of image coverage, penetration depth and noise correlations between elements. Vessel wall of a common carotid section was delineated manually. Subsequently, images were assessed based on vessel wall morphology and image quality parameters. The morphological parameters consisted of the vessel wall area, thickness, and normalized wall index (wall area/total vessel area). Image quality parameters consisted of vessel wall SNR, wall-lumen contrast-to-noise ratio (CNR), the vessel g-factor, and CNRindex ((wall-lumen signal) / (wall+lumen signal)). Repeated measures analysis of variance (rmANOVA) was applied for each parameter for the averaged 10 slices for all volunteers to assess effect of coil and SENSE factor. If the rmANOVA was significant, post-hoc comparisons were conducted. No significant coil effect were found for vessel wall morphological parameters. SENSE acceleration affected some morphological parameters for 6- and 8-channel coils, but had no effect on the 30-channel coil. The 30-channel coil achieved high acceleration factors (10x) with significantly lower vessel g-factor values (ps ≤ 0.01), but lower vessel wall SNR and CNR values (ps ≤ 0.01). All four coils were capable of high-quality carotid MRI. The 30-channel coil is recommended when rapid image acquisition acceleration is required for 3D measurements, whereas 6- and 8-channel coils demonstrated the highest SNR performance.

Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.

Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA. In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses. All KOOS subscales ('pain', 'symptoms', 'daily activities', 'sports' and 'quality of life') and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee. Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.

Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and allows early interventions to improve engraftment and outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34+ cells, with 19F-containing PLGA nanoparticles which were detectable with both flow cytometry and magnetic resonance spectroscopy (MRS). In addition, labeled CD34+ cells maintain their capacity to proliferate and differentiate, which is pivotal for successful engraftment after transplantation in vivo. These results set the stage for in vivo tracking experiments, through which the homing efficiency of transplanted cells can be studied.

Objectives To evaluate the effect of automated registration in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of the knee on the occurrence of movement artefacts on the T1 map and the reproducibility of region-of-interest (ROI)-based measurements. Methods Eleven patients with early-stage knee osteoarthritis and ten healthy controls underwent dGEMRIC twice at 3 T. Controls underwent unenhanced imaging. ROIs were manually drawn on the femoral and tibial cartilage. T1 calculation was performed with and without registration of the T1-weighted images. Automated three-dimensional rigid registration was performed on the femur and tibia cartilage separately. Registration quality was evaluated using the square root Cramér–Rao lower bound (CRLB σ ). Additionally, the reproducibility of dGEMRIC was assessed by comparing automated registration with manual slice-matching. Results Automated registration of the T1-weighted images improved the T1 maps as the 90% percentile of the CRLB σ was significantly ( P  < 0.05) reduced with a median reduction of 55.8 ms (patients) and 112.9 ms (controls). Manual matching and automated registration of the re-imaged T1 map gave comparable intraclass correlation coefficients of respectively 0.89/0.90 (patients) and 0.85/0.85 (controls). Conclusions Registration in dGEMRIC reduces movement artefacts on T1 maps and provides a good alternative to manual slice-matching in longitudinal studies. Key Points • Quantitative MRI is increasingly used for biomedical assessment of knee articular cartilage • Image registration leads to more accurate quantification of cartilage quality and damage • Movement artefacts in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are reduced • Automated image registration successfully aligns baseline and follow-up dGEMRIC examinations • Reproducibility of dGEMRIC with registration is similar to that using manual slice-matching

Objectives To assess (1) whether normal and degenerated menisci exhibit different T1 GD on delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM), (2) the reproducibility of dGEMRIM and (3) the correlation between meniscus and cartilage T1 GD in knee osteoarthritis (OA) patients. Methods In 17 OA patients who underwent dGEMRIM twice within 7 days, meniscus and cartilage T1 GD was calculated. Meniscus pathology was evaluated on conventional MRI. T1 GD in normal and degenerated menisci were compared using a Student’s t -test. Reproducibility was assessed using ICCs. Pearson’s correlation was calculated between meniscus and cartilage T1 GD . Results A trend towards lower T1 GD in degenerated menisci (mean: 402 ms; 95 % CI: 359–444 ms) compared to normal menisci (mean: 448 ms; 95 % CI: 423–473 ms) was observed ( p  = 0.05). Meniscus T1 GD ICCs were 0.85–0.90. The correlation between meniscus and cartilage T1 GD was moderate in the lateral ( r  = 0.52–0.75) and strong in the medial compartment ( r  = 0.78–0.94). Conclusions Our results show that degenerated menisci have a clear trend towards lower T1 GD compared to normal menisci. Since these results are highly reproducible, meniscus degeneration may be assessed within one delayed gadolinium-enhanced MRI simultaneously with cartilage. The strong correlation between meniscus and cartilage T1 GD suggests concomitant degeneration in both tissues in OA, but also suggests that dGEMRIC may not be regarded entirely as sulphated glycosaminoglycan specific. Key Points • dGEMRIM T1 GD can possibly be used to assess meniscal degeneration; • dGEMRIM yields highly reproducible meniscal T1 GD in early stage osteoarthritic patients; • Concomitant degeneration of cartilage and meniscus tissue occurs in early stage osteoarthritis; • dGEMRIC cannot be regarded as entirely sulphated glycosaminoglycan specific.

Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and allows early interventions to improve engraftment and outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34.sup.+ cells, with .sup.19 F-containing PLGA nanoparticles which were detectable with both flow cytometry and magnetic resonance spectroscopy (MRS). In addition, labeled CD34.sup.+ cells maintain their capacity to proliferate and differentiate, which is pivotal for successful engraftment after transplantation in vivo. These results set the stage for in vivo tracking experiments, through which the homing efficiency of transplanted cells can be studied.

An increasing amount of recent research has demonstrated that the hexosamine biosynthesis pathway (HBP) plays a significant role in the modulation of intracellular signaling transduction pathways, and affects cellular processes via modification of protein by O-linked β-N-acetylglucosamine (O-GlcNAc). Besides the many known and postulated effects of protein O-GlcNAc modifications, there is little available data on the role of O-GlcNAc in cellular volume regulation. Our objective was to test the effect of increased O-GlcNAc levels on hypotonia-induced volume changes in Jurkat cells. We pretreated Jurkat cells for 1 h with glucosamine (GlcN), PUGNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene)-amino-N-phenylcarbamate) an inhibitor of O-GlcNAcase, or a high level of glucose to induce elevated levels of O-GlcNAc. We found that the response of Jurkat cells to hypotonic stress was significantly altered. The hypotonia induced cell-swelling was augmented in both GlcN and PUGNAc-treated cells and, to a lesser extent, in high glucose concentration-treated cells. Evaluated by NMR measurements, GlcN and PUGNAc treatment also significantly reduced intracellular water diffusion. Taken together, increased cell swelling and reduced water diffusion caused by elevated O-GlcNAc show notable analogy to the regulatory volume changes seen by magnetic resonance methods in nervous and other tissues in different pathological states. In conclusion, we demonstrate for the first time that protein O-GlcNAc could modulate cell volume regulation.

Vizsgálataink a stroke során felmerülő radiológiai probléma nyomán azt a célt tűzték ki, hogy ellenőrizhető modellkísérletekben a víz diffúziós tényezőjének és a T2 relaxációs időnek a kontrollálható paraméterektől való függését felderítsék. A vizsgálatok tárgyát kísérleti modell-oldatok, illetve sejtek szuszpenziói képezték. A kísérleti eredmények elméleti modellekkel vetettem össze, ennek célja a következő volt: a) a modellek érvényességét tesztelni, b) a validált modellek alapján összetett rendszerekben bekövetkező diffúziós tényező és T2 relaxációs idő változásokat megjósolni, c) az MR mérések tér-, és időskáláját illetően koherens képet kialakítani, amely támpontot ad a diagnosztika szakemberei számára. Vizsgálataim középpontjában heterogén (intra-, és extracelluláris közeget is tartalmazó) rendszerek diffúziós és relaxációs tulajdonságai álltak. Az intra-, és extracelluláris tér oldott molekulái minőségének és mennyiségének hatását vizsgáltam.Proteolízis modell kísérletekEgy homogén mintában a diffúziós és relaxációs tulajdonságokat a víz és az oldott anyag molekulái közötti kölcsönhatások határozzák meg. A molekuláris történések (proteinek degradálódása, polimerizációs folyamatok), valamint a koncentráció-változások egyszerre jelenhetnek meg élettani folyamatokban. E történések egymástól független hatásának vizsgálata állt a modell-kísérletek középpontjában.Molekuláris crowding kísérletekA VVT fehérjeállománya 95%-ban hemoglobin. A különböző fajok hemoglobinja eltérő hidrofilitású aminosavakat tartalmaz. Az intracelluláris tér molekuláinak vízzel való kölcsönhatása fajonkénti különbözik. E kísérletek célja az extracelluláris tértől mentesnek mondható vörösvértest (VVT) masszák MR vizsgálatának és a minták ozmotikus viselkedésének összevetése volt. Az oldatkísérletekkel és a heterogén rendszereken végzett kísérletekkel való összehasonlításban a sejtfalak diffúziót gátló hatása meghatározható. Intracelluláris (IC) és extracelluláris (EC) tér hatásának független vizsgálataAz IC és EC tér koncentrációjának és oldott molekulái minőségének hatását vizsgáltuk VVT szuszpenziókon. Az EC tér koncentrációjának és az oldott molekulák minőségének hatását, valamint az IC tér koncentrációjának hatását vizsgáltuk. Célul tűztük ki olyan elméleti modell kiválasztását, amely a kísérleti eredményeket helyesen írja le. Ezek a kísérletek vezetnek a szövetekben tapasztalt MR eredmények értelmezéséhez, a heterogén közegek MR mérések által meghatározott idő-, és térskálájú viselkedésének leírásához.