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.

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.

Dental pulp mesenchymal stem/stromal cells labeled with iron sucrose release exosomes and cells applied intra-nasally migrate to intracerebral glioblastoma.

We report on a simple iron oxide (Venofer) labeling procedure of dental pulp mesenchymal stem cells (DP-MSCs) and DP-MSCs transduced with yeast cytosinedeaminase::uracilphosphoribosyltransferase (yCD::UPRT-DP-MSCs). Venofer is a drug approved for intravenous application to treat iron deficiency anemia in patients. Venofer labeling did not affect DP-MSCs or yCD::UPRT-DP-MSCs viability and growth kinetics. Electron microscopy of labeled cells showed internalized Venofer nanoparticles in endosomes. MRI relativity measurement of Venofer labeled DP-MSCs in a phantom arrangement revealed that 100 cells per 0.1 ml were still detectable. DP-MSCs or yCD::UPRT-DP-MSCs and the corresponding Venofer labeled cells release exosomes into conditional medium (CM). CM from yCD::UPRT-DP-MSCs in the presence of a prodrug 5-fluorocytosine caused tumor cell death in a dose dependent manner. Iron labeled DP-MSCs or yCD::UPRT-DP-MSCs sustained their tumor tropism in vivo; intra-nasally applied cells migrated and specifically engrafted orthotopic glioblastoma xenografts in rats.

Brain tumours at 7T MRI compared to 3T--contrast effect after half and full standard contrast agent dose: initial results.

OBJECTIVES: To compare the contrast agent effect of a full dose and half the dose of gadobenate dimeglumine in brain tumours at 7 Tesla (7 T) MR versus 3 Tesla (3T). METHODS: Ten patients with primary brain tumours or metastases were examined. Signal intensities were assessed in the lesion and normal brain. Tumour-to-brain contrast and lesion enhancement were calculated. Additionally, two independent readers subjectively graded the image quality and artefacts. RESULTS: The enhanced mean tumour-to-brain contrast and lesion enhancement were significantly higher at 7 T than at 3T for both half the dose (91.8 ± 45.8 vs. 43.9 ± 25.3 [p = 0.010], 128.1 ± 53.7 vs. 75.5 ± 32.4 [p = 0.004]) and the full dose (129.2 ± 50.9 vs. 66.6 ± 33.1 [p = 0.002], 165.4 ± 54.2 vs. 102.6 ± 45.4 [p = 0.004]). Differences between dosages at each field strength were also significant. Lesion enhancement was higher with half the dose at 7 T than with the full dose at 3T (p = .037), while the tumour-to-brain contrast was not significantly different. Subjectively, contrast enhancement, visibility, and lesion delineation were better at 7 T and with the full dose. All parameters were rated as good, at the least. CONCLUSION: Half the routine contrast agent dose at 7 T provided higher lesion enhancement than the full dose at 3T which indicates the possibility of dose reduction at 7 T. KEY POINTS: • The contrast effect of gadobenate dimeglumine was assessed at 7 T and 3T. • In brain tumours, contrast effect was higher at 7 T than at 3T. • Tumour-to-brain contrast at 7 T half dose and 3T full dose were comparable. • 7 T half dose lesion enhancement was higher than 3T full dose enhancement. • Our results indicate the possibility of contrast agent dose reduction at 7 T.

Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience.

OBJECTIVE: To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. METHODS: Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. RESULTS: Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). CONCLUSIONS: Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy.

Parallel imaging of the cervical spine at 3T: optimized trade-off between speed and image quality.

BACKGROUND AND PURPOSE: Patients with cervical spine syndrome often experience pain during the MR examination. Our aim was to compare the quality of cervical spine MR images obtained by parallel imaging with those of nonaccelerated images, with the goal of shortening the examination time while preserving adequate image quality. MATERIALS AND METHODS: A phantom study and examinations of 10 volunteers and 26 patients were conducted on a clinical 3T scanner. Acquisitions included axial T2WI, sagittal T2WI, T1WI, and T2TIRM sequences. Nonaccelerated sequences and accelerated sequences with different numbers of averages and different accelerations, with a scanning time reduction of 67%, were performed. For quantitative analysis, the SNR was obtained from the phantom measurements, and the NU was calculated from the volunteer measurements. For qualitative analysis, 3 independent readers assessed the delineation of anatomic structures in volunteers and the visibility of degenerative disease in patients. RESULTS: In the phantom study, as expected, the SNR of the nonaccelerated images was higher than the SNR of the same sequence with parallel imaging. In vivo, the NU was higher when applying fewer averages or parallel imaging, compared with the nonaccelerated images. The analysis of the subjective parameters in the volunteers and patients showed that a scanning time of 48% of the original protocol could be obtained by combining the following sequences: sagittal T1WI with 1 average; sagittal T2WI with acceleration factor 3; sagittal T2TIRM with acceleration factor 2; and axial T2* GRE with acceleration factor 2. CONCLUSIONS: Parallel imaging of the cervical spine at 3T allows shortening of the examination time by 52%, preserving adequate image quality.

Detection of degenerative cartilage disease: comparison of high-resolution morphological MR and quantitative T2 mapping at 3.0 Tesla.

OBJECTIVE: The aim of the study was to investigate the association of T2 relaxation times of the knee with early degenerative cartilage changes. Furthermore the impact of unloading the knee on T2 values was evaluated. METHODS: Forty-three patients with knee pain and an ICRS (International Cartilage Repair Society) cartilage defect grade

T2 mapping and dGEMRIC after autologous chondrocyte implantation with a fibrin-based scaffold in the knee: preliminary results.

OBJECTIVE: To assess repair tissue (RT) after the implantation of BioCartII, an autologous chondrocyte implantation (ACI) technique with a fibrin-hyaluronan polymer as scaffold. T2 mapping and delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) were used to gain first data on the biochemical properties of BioCartII RT in vivo. METHODS: T2 mapping and dGEMRIC were performed at 3T in five patients (six knee joints) who had undergone ACI 15-27 months before. T2 maps were obtained using a pixel wise, mono-exponential non-negative least squares fit analysis. For quantitative T1 mapping a dual flip angle 3D GRE sequence was used and T1 maps were calculated pre- and post-contrast using IDL software. Subsequent region of interest analysis was carried out in comparison with morphologic MRI. RESULTS: A spatial variation of T2 values in both hyaline, normal cartilage (NC) and RT was found. Mean RT T2 values and mean NC T2 values did not differ significantly. Relative T2 values were calculated from global RT and NC T2 and showed a small range (0.84-1.07). The relative delta relaxation rates (rDeltaR1) obtained from the T1 maps had a wider range (0.77-4.91). CONCLUSION: T2 mapping and dGEMRIC provided complementary information on the biochemical properties of the repair tissue. BioCartII apparently can provide RT similar to hyaline articular cartilage and may become a less-invasive alternative to ACI with a periosteal flap.

High-field, high-resolution, susceptibility-weighted magnetic resonance imaging: improved image quality by addition of contrast agent and higher field strength in patients with brain tumors.

INTRODUCTION: To demonstrate intratumoral susceptibility effects in malignant brain tumors and to assess visualization of susceptibility effects before and after administration of the paramagnetic contrast agent MultiHance (gadobenate dimeglumine; Bracco Imaging), an agent known to have high relaxivity, with respect to susceptibility effects, image quality, and reduction of scan time. METHODS: Included in the study were 19 patients with malignant brain tumors who underwent high-resolution, susceptibility-weighted (SW) MR imaging at 3 T before and after administration of contrast agent. In all patients, Multihance was administered intravenously as a bolus (0.1 mmol/kg body weight). MR images were individually evaluated by two radiologists with previous experience in the evaluation of pre- and postcontrast 3-T SW MR images with respect to susceptibility effects, image quality, and reduction of scan time. RESULTS: In the 19 patients 21 tumors were diagnosed, of which 18 demonstrated intralesional susceptibility effects both in pre- and postcontrast SW images, and 19 demonstrated contrast enhancement in both SW images and T1-weighted spin-echo MR images. Conspicuity of susceptibility effects and image quality were improved in postcontrast images compared with precontrast images and the scan time was also reduced due to decreased TE values from 9 min (precontrast) to 7 min (postcontrast). CONCLUSION: The intravenous administration of MultiHance, an agent with high relaxivity, allowed a reduction of scan time from 9 min to 7 min while preserving excellent susceptibility effects and image quality in SW images obtained at 3 T. Contrast enhancement and intralesional susceptibility effects can be assessed in one sequence.

High-resolution contrast-enhanced, susceptibility-weighted MR imaging at 3T in patients with brain tumors: correlation with positron-emission tomography and histopathologic findings.

BACKGROUND AND PURPOSE: The purpose of this work was to demonstrate susceptibility effects (SusE) in various types of brain tumors with 3T high-resolution (HR)-contrast-enhanced (CE)-susceptibility-weighted (SW)-MR imaging and to correlate SusE with positron-emission tomography (PET) and histopathology. MATERIALS AND METHODS: Eighteen patients with brain tumors, scheduled for biopsy or tumor extirpation, underwent high-field (3T) MR imaging. In all of the patients, an axial T1-spin-echo (SE) sequence and an HR-SW imaging sequence before and after IV application of a standard dose of contrast agent (MultiHance) was obtained. Seven patients preoperatively underwent PET. The frequency and formation of intralesional SusE in all of the images were evaluated and correlated with tumor grade as determined by PET and histopathology. Direct correlation of SusE and histopathologic specimens was performed in 6 patients. Contrast enhancement of the lesions was assessed in both sequences. RESULTS: High-grade lesions demonstrated either high or medium frequency of SusE in 90% of the patients. Low-grade lesions demonstrated low frequency of SusE or no SusE. Correlation between intralesional frequency of SusE and histopathologic, as well as PET, tumor grading was statistically significant. Contrast enhancement was equally visible in both SW and SE sequences. Side-to-side comparison of tumor areas with high frequency of SusE and histopathology revealed that intralesional SusE reflected conglomerates of increased tumor microvascularity. CONCLUSIONS: 3T HR-CE-SW-MR imaging shows both intratumoral SusE not visible with standard MR imaging and contrast enhancement visible with standard MR imaging. Because frequency of intratumoral SusE correlates with tumor grade as determined by PET and histopathology, this novel technique is a promising tool for noninvasive differentiation of low-grade from high-grade brain tumors and for determination of an optimal area of biopsy for accurate tumor grading.

MR imaging of osteochondral grafts and autologous chondrocyte implantation.

Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible.

Transverse relaxation mechanisms in articular cartilage.

Relaxation rates in the rotating frame (R1rho) and spin-spin relaxation rates (R2) were measured in articular cartilage at various orientations of cartilage layer to the static magnetic field (B0), at various spin locking field strengths and at two different static magnetic field strengths. It was found that R1rho in the deep radial zone depended on the orientation of specimens in the magnet and decreased with increasing the spin locking field strength. In contrast, R1rho values in the transitional zone were nearly independent of the specimen orientation and the spin locking field strength. Measurements of the same specimens at 2.95 and 7.05 T showed an increase of R1rho and most R2 values with increasing B0. The inverse B0 dependence of some R2 values was probably due to a multicomponent character of the transverse magnetization decay. The experiments revealed that the dominant T1rho and T2 relaxation mechanism at B0 < or = 3 T is a dipolar interaction due to slow anisotropic motion of water molecules in the collagen matrix. On average, the contribution of scalar relaxation due to rapid proton exchange in femoral head cartilage at 2.95 T is about 6% or less of the total R1rho at the spin locking field of 1000 Hz.

SPIRAL-SPRITE: a rapid single point MRI technique for application to porous media.

This study presents the application of a new, rapid, single point MRI technique which samples k space with spiral trajectories. The general principles of the technique are outlined along with application to porous concrete samples, solid pharmaceutical tablets and gas phase imaging. Each sample was chosen to highlight specific features of the method.

Short-TE projection reconstruction NMR microscopy of trabecular bone.

The aim of this study was to assess the potential of projection reconstruction (PR) NMR microscopy in the quantitative evaluation of trabecular bone architecture. Short-TE PR spin-echo microimages were acquired at 7.05 T on normal bone explants. The main structural parameters such as bone volume fraction (BVF), trabecular thickness (Tb.Th.) and trabecular separation (Tb.Sp.) were obtained from the 3D microimages using the method of directed secants. Quantitative structural data were then compared with those derived from conventional spin-echo microimages. Our study indicates that projection reconstruction NMR microscopy promises to be more accurate than the conventional FTI method in the analysis of trabecular bone.

Proteoglycan depletion and magnetic resonance parameters of articular cartilage.

Calcium ions and various amounts of proteoglycans were removed from porcine articular cartilage explants using ethylenediaminetetraacetic acid or guanidinium chloride solutions. The water proton magnetic parameters such as T(1) and T(2) relaxation times, diffusion (D), and magnetization transfer (M(S)/M(0)) were then measured by 1D MR microscopy on native specimens, after incubation in the extracting solutions and after final reconditioning in a physiological saline. While the replacement of the interstitial fluid by the treating solutions strongly affected the various MR parameters, calcium depletion did not show any influence on the MRI appearance of the chondral tissue. Interestingly, only the longitudinal relaxation time T(1) and the diffusion coefficient D were seen to be sensitive to an extensive proteoglycan depletion of the tissue. Our results indicate that a modest proteoglycan depletion, as it occurs in the early stage of a pathological cartilage degradation, has little relevance to the above MR parameters. Further MRI studies on the macromolecular components of cartilage are, therefore, necessary for a better understanding of the interaction mechanisms between water and extracellular matrix that might lead to the early diagnosis of the cartilage damage.

High-resolution spectroscopic imaging of the human skin.

High-resolution water, fat and chemical shift artefact-free images of different areas of the skin were obtained on a whole-body MR unit (1.5 T) with commercial receiver surface coil with a diameter of 25 mm and high-power gradients (23 mT/m). Sufficient signal-to-noise ratio was achieved by lowering receiver bandwidth to +/-10 kHz or lower and shortening the echo time to 11 (13) ms. Spectroscopic image data sets were acquired with resolution 0.102 x 0.133 mm in plane and slice thickness 0.5 mm. The results demonstrate that it is possible to produce high-quality water and fat micro-images of the skin layers using only a few chemical shift encoding steps in a clinically reasonable time (approximately 2 minutes per slice).

Short-TE projection reconstruction MR microscopy in the evaluation of articular cartilage thickness.

The aim of this study was to assess the potential of projection-reconstruction (PR) MR microscopy in the accurate measurement of cartilage thickness. Short-TE PR microimages were acquired at 7.05 T on bone-cartilage cylindrical plugs excised from four regions of two disarticulated femoral heads (i. e. superior, inferior, posterior and anterior), using an NMR instrument equipped with a microimaging accessory. The PR microimages were then correlated with conventional spin-echo (SE) microimages and with histology. On PR microimages, acquired with an echo time of 3.2 ms, the cartilage signal was increased, allowing an accurate delineation of the cartilage from the tidemark/cortical bone region. As a consequence, by the PR method a more precise measurement of cartilage thickness compared with that performed by the conventional SE approach was feasible. An excellent correlation between PR microimages and histology was also obtained (r = 0.90). By the proposed method it is possible to accurately determine the cartilage thickness better than with the conventional SE sequences.