Magnetic Resonance Imaging Microscopy Research Articles

Assessment of articular cartilage degradation in response to an impact injury using µMRI

ABSTRACT Purpose Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. Materials and methods A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. Results The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2–55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. Conclusions This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage.

A cryogenic tune and match circuit for magnetic resonance microscopy at 15.2T

Background and SignificanceAchievable signal to noise ratios (SNR) in magnetic resonance microscopy images are limited by acquisition times and the decreasing number of spins in smaller voxels. A common method of enhancing SNR is to cool the RF receiver coil. Significant SNR gains are realized only when the Johnson noise generated within the RF hardware is large compared to the electromagnetic noise produced by the sample. Cryogenic cooling of imaging probes is in common use in high field systems, but it is difficult to insulate a sample from the extreme temperatures involved and in practice imaging cryoprobes have been limited to surface or partial volume designs only. In order to use a solenoid in which the windings were not directly cooled and in close proximity to the sample, we designed a chamber to cool only the tune and match circuitry and show experimentally it is possible to achieve much of the theoretically available SNR gain. MethodsA microcoil circuit consisting of two tuning capacitors, one fixed capacitor, and SMB coaxial cable was designed to resonate at 650 MHz for imaging on a Bruker 15.2 T scanner. Sample noise increases with the sample diameter, so surface loops and solenoids of varying diameters were tested on the bench to determine the largest diameter coil that demonstrated significant SNR gains from cooling. A liquid N2 cryochamber was designed to cool the tune and match circuit, coaxial cable, and connectors, while leaving the RF coil in ambient air. As the cryochamber was filled with liquid N2, quality factors were measured on the bench while monitoring the coil's surface temperature. Improvements of SNR on images of ionic solutions were demonstrated via cooling the tune and match circuit in the magnet bore. ResultsAt 650 MHz, loops and solenoids < 3 mm in diameter showed significant improvements in quality factor on the bench. The resistance of the variable capacitors and the coaxial cable were measured to be 45% and 32% of room temperature values near the Larmor frequency. Images obtained with a 2 turn, 3 mm diameter loop with the matching circuit at room temperature and then cooled with liquid nitrogen demonstrated SNR improvements of a factor of 2. ConclusionsBy cooling the tune and match circuit and leaving the surface loop in ambient air, SNR was improved by a factor of 2. The results are significant because it allows for more space to insulate the sample from the extreme temperatures used in imaging cryoprobes.

Characteristics of distal femoral articular cartilage in 6 weeks posttraumatic osteoarthritis by a subcritical impact.

Traumatized knee greatly contributes to osteoarthritis (OA) of the knee in young adults. To intervene effectively before the onset of severe structural disruption, detection of the disease at the early onset is crucial. In this study, we put together the findings for the detection of OA from the femoral knee joint cartilage of the rabbit at 6 weeks posttrauma. Articular cartilage samples are taken from the impacted and nonimpacted joints at 0 week (serving as the control group) and at 6 weeks posttrauma by minimal force. The samples were imaged using microscopic magnetic resonance imaging (µMRI) at 11.7 µm/pixel and polarized light microscopy (PLM) at 1 µm/pixel. In addition, an inductively coupled plasma - optical emission spectrometry analysis was performed using the adjacent cartilage samples. The outcomes of this study demonstrate an increase in T2 values in 6 weeks samples compared to the 0 week samples by µMRI technique, indicating a general increase of tissue hydration within cartilage. PLM detects a decrease in the average thickness of the superficial zones in the posttraumatic osteoarthritis samples, significant in the impacted femurs. There was an average increasing trend of maximum retardation in the tide mark in comparison to the reported calcium concentration (mg/L) in impacted samples suggesting a possible rise in mineralization in the 6 weeks samples. Qualitatively, physical observation of the joint after 6 weeks showed signs of reddening in the anterior femur suggesting the disease process is a localized phenomenon. Through microscopic imaging, we are able to detect these changes at 6 weeks posttrauma qualitatively and quantitatively.

A unified 3D map of microscopic architecture and MRI of the human brain.

We present the first three-dimensional (3D) concordance maps of cyto- and fiber architecture of the human brain, combining histology, immunohistochemistry, and 7-T quantitative magnetic resonance imaging (MRI), in two individual specimens. These 3D maps each integrate data from approximately 800 microscopy sections per brain, showing neuronal and glial cell bodies, nerve fibers, and interneuronal populations, as well as ultrahigh-field quantitative MRI, all coaligned at the 200-μm scale to the stacked blockface images obtained during sectioning. These unprecedented 3D multimodal datasets are shared without any restrictions and provide a unique resource for the joint study of cell and fiber architecture of the brain, detailed anatomical atlasing, or modeling of the microscopic underpinnings of MRI contrasts.

Median and ulnar nerve fascicle imaging using MR microscopy and high-resolution ultrasound.

Understanding nerve microanatomy is important as different neuropathies and some nerve neoplasms present with fascicle enlargement. The aim of our study was to gain clinically oriented knowledge on nerve fascicular anatomy using imaging modalities. On a cadaveric upper extremity, high-resolution ultrasound (HRUS) scan with 22MHz probe was performed. Sections of the median and ulnar nerves were excised at the level of the distal arm and after magnetic resonance microscopy (MRM), histological cross-sections (HCS) were prepared. Cross-referencing of the MRM and HRUS images with HCS was performed. Fascicle and nerve contouring was performed with morphometric software in order to assess nerve and fascicular cross-sectional area (CSA), fascicle count, and interfascicular distances. Based on fascicle differentiation, factual fascicle (FF) group and fascicular cluster (FC) group were defined. On the cross-referenced imaging material, fascicles were differentiated in 92.7% on MRM and in 57.3% on HRUS. High to very high positive correlation among imaging material was observed for the fascicle CSA. FF depiction was 30.1% on HRUS. In comparison to the FF group, the FC group had significantly larger fascicle CSA and shorter interfascicular distances. The findings of our study contribute to understanding of fascicle depiction on imaging modalities. HRUS offers good visualization of fascicles. The capability of differentiating fascicles is modality specific and depends on the fascicle CSA and the amount of interfascicular epineurium.

Multiturn Planar Inductor for the Improvement of Signal-to-Noise Ratio Response in Magnetic Resonance Microscopy

In this study, we propose a novel, multiturn histology coil for microscopic magnetic resonance (MR) imaging of histological tissue slices with substantially higher signal-to-noise-ratio (SNR) outcomes compared with previously developed coils. We performed electromagnetic simulations of the proposed coils and acquired MR images from a gelatin phantom and a rat brain slice with the implemented coils. The performances of the coils were evaluated by comparing the measured and simulated radio-frequency transmission (B₁⁺) fields in a flip-angle map form, and with low flip-angle gradient echo images to calculate the SNR increase as a function of the number of turns (<i>n</i>) of the coils. This study was performed on a 3 T MR imaging system. The proposed coil with <i>n</i> = 7 achieved SNR greater than 3.5 times that of a single-turn coil while preserving the highly uniform B₁⁺ field across the imaging region. The proposed method provides new possibilities for high-resolution MR imaging of microscopic tissue samples for biomedical applications.

Location-Specific Study of Young Rabbit Femoral Cartilage by Quantitative µMRI and Polarized Light Microscopy.

ObjectiveMicroscopic magnetic resonance imaging (µMRI) and polarized light microscopy (PLM) are used to characterize the structural variations at different anatomical locations of femoral cartilage in young rabbits (12-14 weeks old).DesignFour intact knees were imaged by µMRI at 86 µm resolution. Three small cartilage-bone specimens were harvested from each of 2 femoral medial condyles and imaged by quantitative µMRI (T2 anisotropy) at 9.75 µm resolution (N = 6). These specimens, as well as the other 2 intact femoral condyles, were used for histology and imaged by quantitative PLM (retardation and angle) at 0.25 µm to 4 µm resolutions.ResultsQuantitative MRI relaxation data and PLM fibril data revealed collaboratively distinct topographical variations in both cartilage thickness and its collagen organization in the juvenile joint. Cartilage characteristics from the central location have a 3-zone arcade-like fibril structure and a distinct magic angle effect, commonly seen in mature articular cartilage, while cartilage at the anterior location lacks these characteristics. Overall, the lowest retardation values and isotropic T2 values have been found in the distal femur (trochlear ridge), with predominant parallel fibers with respect to the articular surface. Central cartilage is the thickest (~550 µm), approximately twice as thick as the anterior and posterior locations.ConclusionDistinctly different characteristics of tissue properties were found in cartilage at different topographical locations on femoral condyle in rabbits. Knowledge of location-specific structural differences in the collagen network over the joint surface can improve the understanding of local mechanobiology and provide insights to tissue engineering and degradation repairs.

Validation study of novel grading system for ulnar collateral ligament injury of the elbow with high-resolution magnetic resonance imaging.

BackgroundRecently, magnetic resonance imaging (MRI) classification of medial ulnar collateral ligament (UCL) tears has been introduced, but little is known about the relationship between MRI grading and medial joint laxity. It has been reported that microscopy coils could make it possible to achieve high-resolution images of upper extremities with a superior diagnostic ability to conventional MRI. However, there is no report that has compared the diagnostic reliability between microscopic and conventional MRI. The purpose of this study was to assess the relationship between MRI findings and medial joint laxity evaluated with stress ultrasound (US). Secondary objective was to compare the reliabilities of UCL evaluation between microscopic and conventional MRI.MethodsOne-hundred thirty baseball players who underwent MRI of the elbow for the diagnosis of UCL injury using both conventional and microscopy MRI were included in this study. They also underwent stress US for assessment of medial joint laxity against valgus stress. Our MRI grading system for UCL injuries was compared to medial joint laxity evaluated with stress US. The intrarater and interrater reliabilities of our grading system were assessed with both microscopic and conventional MRI.ResultsOur grading system was related to valgus stability, especially with microscopic MRI. The reliabilities were fair when combined with microscopic MRI, which exhibited better intrarater and interrater reliabilities than conventional MRI.ConclusionHigh-resolution microscopic MRI may contribute to the accurate diagnosis of UCL injuries.

Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging

IntroductionIn this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy.Materials and methodsThe study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model.ResultsBetween June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001).ConclusionME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients.Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

The endosperm cavity of wheat grains contains a highly hydrated gel of arabinoxylan

Cereal grains provide a substantial part of the calories for humans and animals. The main quality determinants of grains are polysaccharides (mainly starch but also dietary fibers such as arabinoxylans, mixed-linkage glucans) and proteins synthesized and accumulated during grain development in a specialized storage tissue: the endosperm.In this study, the composition of a structure localized at the interface of the vascular tissues of the maternal plant and the seed endosperm was investigated. This structure is contained in the endosperm cavity where water and nutrients are transferred to support grain filling. While studying the wheat grain development, the cavity content was found to autofluoresce under UV light excitation. Combining multispectral analysis, Fourier-Transform infrared spectroscopy, immunolabeling and laser-dissection coupled with wet chemistry, we identified in the cavity arabinoxylans and hydroxycinnamic acids. The cavity content forms a “gel” in the developing grain, which persists in dry mature grain and during subsequent imbibition. Microscopic magnetic resonance imaging revealed that the gel is highly hydrated.Our results suggest that arabinoxylans are synthesized by the nucellar epidermis, released in the cavity where they form a highly hydrated gel which might contribute to regulate grain hydration.

Structural Morphology of Rabbit Patella and Suprapatella Cartilage by Microscopic MRI and Polarized Light Microscopy.

In order to appreciate the roles articular cartilage of sesamoid bones and sesamoid fibrocartilage play in anatomy and pathology, the articular cartilage of the patella (n = 4) and suprapatella (n = 4) (a sesamoid fibrocartilage) of 12 to 14 weeks old New Zealand rabbits were studied qualitatively and quantitatively. The intact knee joints and block specimens from the joints were imaged using microscopic magnetic resonance imaging (µMRI) at a 97.6-µm pixel resolution for the former and 19.5-µm resolution for the latter. Histological sections were made out of the µMRI-imaged specimens, which were imaged using polarized light microscopy (PLM) at 0.25-, 1-, and 4-µm pixel resolutions. The patella cartilage varied in thickness across the medial to lateral ends of the sesamoid bone with the central medial aspect slightly thicker than the lateral aspect. The suprapatella fibrocartilage decreased proximally away from the knee joint. Quantitative results of patellar cartilage showed strong dependence of fiber orientation with the tissue depth. Three histological zones can be clearly observed, which are similar to articular cartilage from other large animals. The sesamoid fibrocartilage has one thin surface layer (10 µm thick) of parallel-arranged structured fibers followed immediately by the majority of random fibers in bulk tissue. T2 relaxation time anisotropy was observed in the patellar cartilage but not in the bulk fibrocartilage. Given the different functions of these 2 different types of cartilages in joint motion, these quantitative results will be beneficial to future studies of joint diseases using rabbits as the animal model.

Intrinsic microstructural anisotropy in tape cast ceramics by ice templating

AbstractIce templating concepts based on tape cast processing technology are capable of creating continuous columnar‐graded pore structures using a wide variety of ceramic oxides with thicknesses from 100 µm up to 1 cm for applications including fuel cells, compositional grading templates, filtration/separation membranes, and catalyst supports. The merging of the tape casting process allows for the preparation of large area flexible green tapes as well as the long‐range alignment of the acicular ice crystals transverse to the cross‐section, yielding an additional degree of microstructure control beyond traditional freeze cast processing. Moreover, optimization of the freeze tape casting processing parameters has proven effective in tailoring porosity in aqueous cast ceramics. Magnetic resonance microscopy (MRM) combined with scanning electron microscopy (SEM) has revealed inherent microstructural anisotropy in the morphology of pores related to the direction of the cast tape. Due to the ability of MRM to image noninvasively with volume averaging over a range of slice thicknesses, the MRM images provide complementary information to the higher resolution single plane SEM images. Morphological variance as observed at different orientations through the cross‐sections of cast yttria stabilized zirconia is reported.

Magnetic resonance microscopy and correlative histopathology of the infarcted heart

Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI.

Detection of early osteoarthritis in canine knee joints 3 weeks post ACL transection by microscopic MRI and biomechanical measurement.

Purpose:To detect early osteoarthritis (OA) in a canine Pond–Nuki model 3 weeks after anterior cruciate ligament (ACL) transection surgery, both topographically over the medial tibial surface and depth-dependently over the cartilage thickness.Methods:Four topographical locations on each OA and contralateral medial tibia were imaged individually by magnetic resonance imaging (MRI) at 17.6 μm transverse resolution. The quantitative MRI T2 relaxation data were correlated with the biomechanical stress-relaxation measurements from adjacent locations.Results:OA cartilage was thinner than the contralateral tissue and had a lower modulus compared to the contralateral cartilage for the exterior, interior, and central medial tibia locations. Depth-dependent and topographical variations were detected in OA cartilage by a number of parameters (compressive modulus, glycosaminoglycan concentration, bulk and zonal thicknesses, T2 at 0° and 55° specimen orientations in the magnet). T2 demonstrated significant differences at varying depths between OA and contralateral cartilage.Conclusion:ACL transection caused a number of changes in the tibial cartilage at 3 weeks after the surgery. The characteristics of these changes, which are topographic and depth-dependent, likely reflect the complex degradation in this canine model of OA at the early developmental stage.

Epitope Mapping of SERCA2a Identifies an Antigenic Determinant That Induces Mainly Atrial Myocarditis in A/J Mice.

Sarcoplasmic/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971-990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a 971-990-induced disease was associated with the induction of CD4 T cell responses and the epitope preferentially binds MHC class II/IAk rather than IEk By creating IAk/and IEk/SERCA2a 971-990 dextramers, the T cell responses were determined by flow cytometry to be Ag specific. 3) SERCA2a 971-990-sensitized T cells produce both Th1 and Th17 cytokines. 4) Animals immunized with SERCA2a 971-990 showed Ag-specific Abs with enhanced production of IgG2a and IgG2b isotypes, suggesting that SERCA2a 971-990 can potentially act as a common epitope for both T cells and B cells. 5) Finally, SERCA2a 971-990-sensitized T cells were able to transfer disease to naive recipients. Together, these data indicate that SERCA2a is a critical autoantigen in the mediation of atrial inflammation in mice and that our model may be helpful to study the inflammatory events that underlie the development of conditions such as atrial fibrillation in humans.

Postmortem diffusion MRI of the entire human spinal cord at microscopic resolution.

The human spinal cord is a central nervous system structure that plays an important role in normal motor and sensory function, and can be affected by many debilitating neurologic diseases. Due to its clinical importance, the spinal cord is frequently the subject of imaging research. Common methods for visualizing spinal cord anatomy and pathology include histology and magnetic resonance imaging (MRI), both of which have unique benefits and drawbacks. Postmortem microscopic resolution MRI of fixed specimens, sometimes referred to as magnetic resonance microscopy (MRM), combines many of the benefits inherent to both techniques. However, the elongated shape of the human spinal cord, along with hardware and scan time limitations, have restricted previous microscopic resolution MRI studies (both in vivo and ex vivo) to small sections of the cord. Here we present the first MRM dataset of the entire postmortem human spinal cord. These data include 50 μm isotropic resolution anatomic image data and 100 μm isotropic resolution diffusion data, made possible by a 280 h long multi-segment acquisition and automated image segment composition. We demonstrate the use of these data for spinal cord lesion detection, automated volumetric gray matter segmentation, and quantitative spinal cord morphometry including estimates of cross sectional dimensions and gray matter fraction throughout the length of the cord.

Therapeutic activity of superoxide dismutase-containing enzymosomes on rat liver ischaemia-reperfusion injury followed by magnetic resonance microscopy

Liver ischaemia-reperfusion injury (IRI) may occur during hepatic surgery and is unavoidable in liver transplantation. Superoxide dismutase enzymosomes (SOD-enzymosomes), liposomes where SOD is at the liposomal surface expressing enzymatic activity in intact form without the need of liposomal disruption, were developed with the aim of having a better insight into its antioxidant therapeutic outcome in IRI. We also aimed at validating magnetic resonance microscopy (MRM) at 7T as a tool to follow IRI. SOD-enzymosomes were characterized and tested in a rat ischaemia-reperfusion model and the therapeutic outcome was compared with conventional long circulating SOD liposomes and free SOD using biochemical liver injury biomarkers, histology and MRM. MRM results correlated with those obtained using classical biochemical biomarkers of liver injury and liver histology. Moreover, MRM images suggested that the therapeutic efficacy of both SOD liposomal formulations used was related to prevention of peripheral biliary ductular damage and disrupted vascular architecture. Therefore, MRM at 7T is a useful technique to follow IRI. SOD-enzymosomes were more effective than conventional liposomes in reducing liver ischaemia-reperfusion injury and this may be due to a short therapeutic window.

In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 μm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.

Topographical and depth-dependent glycosaminoglycan concentration in canine medial tibial cartilage 3 weeks after anterior cruciate ligament transection surgery-a microscopic imaging study.

Medical imaging has become an invaluable tool to diagnose damage to cartilage. Depletion of glycosaminoglycans (GAG) has been shown to be one of the early signs of cartilage degradation. In order to investigate the topographical changes in GAG concentration caused by the anterior cruciate ligament transection (ACLT) surgery in a canine model, microscopic magnetic resonance imaging (µMRI) and microscopic computed tomography (µCT) were used to measure the GAG concentration with correlation from a biochemical assay, inductively coupled plasma optical emission spectroscopy (ICP-OES), to understand where the topographical and depth-dependent changes in the GAG concentration occur. This study used eight knee joints from four canines, which were examined 3 weeks after ACLT surgery. From right (n=3) and left (n=1) medial tibias of the ACLT and the contralateral side, two ex vivo specimens from each of four locations (interior, central, exterior and posterior) were imaged before and after equilibration in contrast agents. The cartilage blocks imaged using µMRI were approximately 3 mm × 5 mm and were imaged before and after eight hours submersion in a gadolinium (Gd) contrast agent with an in-plane pixel resolution of 17.6 µm2 and an image slice thickness of 1 mm. The cartilage blocks imaged using µCT were approximately 2 mm × 1 mm and were imaged before and after 24 hours submersed in ioxaglate with an isotropic voxel resolution of 13.4 µm3. ICP-OES was used to quantify the bulk GAG at each topographical location. The pre-contrast µMRI and µCT results did not demonstrate significant differences in GAG between the ACLT and contralateral cartilage at all topographical locations. The post-contrast µMRI and µCT results demonstrated topographically similar significant differences in GAG concentrations between the ACLT and contralateral tibia. Using µMRI, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (54.0±3.6; 70.4±4.3; P=0.001) and interior (54.9±5.9; 71.0±5.9; P=0.029) demonstrated significant differences, but not for the central (61.0±12.0; 67.4±7.2; P=0.438) or posterior (61.6±6.3; 70.3±4.4; P=0.097) locations. Using µCT, the GAG concentrations (mg/mL) were measured for the ACLT and contralateral respectively, the exterior (68.8±0.4; 87.7±4.1; P=0.023) and interior (60.5±9.1; 82.6±8.7; P=0.039) demonstrated significant differences, but not for the central (53.5±5.5; 59.1±25.6; P=0.684) or posterior (52.3±6.2; 61.5±12.7; P=0.325) locations. The depth-dependent GAG (mg/mL) profiles showed significant differences in µMRI for the transitional zone (TZ) [exterior (28.1±4.7; 47.0±8.6; P=0.01) and interior (32.6±4.8; 43.8±8.7; P=0.025)], radial zone (RZ) 1 [exterior (49.6±4.8; 71.5±5.8; P=0.001) and interior (49.4±7.4; 66.7±6.8; P=0.041)], and RZ 2 [exterior (74.9±4.7; 91.8±2.9; P=0.001) and interior (77.1±6.0; 94.8±4.5; P=0.015)], and in µCT for the superficial zone (SZ) [interior (20.6±1.2; 40.4±5.4; P=0.004)], TZ [exterior (45.6±12.0; 61.8±0.5; P=0.049) and interior (36.3±11.7; 60.8±2.0; P=0.019)], and RZ 1 [exterior (61.1±4.1; 85.3±5.6; P=0.039) and interior (53.9±4.9; 78.0±5.1; P=0.041)] for the ACLT and contralateral, respectively. ICP-OES measured significant differences in GAG were found for the exterior (42.1±19.6; 65.3±16.2; P=0.017), central (43.4±4.4; 65.3±10.6; P=0.0111), and interior (46.8±5.6; 61.7±7.3; P=0.0445) but not for the posterior (52.6±12.1; 59.0±2.6; P=0.9252) medial tibia locations compared for the ACLT and contralateral, respectively. The detection and correlation between the three techniques show a topographic depth-dependency on the initial GAG loss in injured cartilage. This topographic and high resolution investigation of ACLT cartilage demonstrated the potential of using µMRI and µCT to study and help diagnose cartilage with very early stages of osteoarthritis.

MR microscopy of the human fetal upper extremity – a proof-of-principle study

BackgroundCurrent knowledge of the human fetal and embryonic development relies on early descriptive studies of humans and from experimental studies of laboratory animals and embryos. Taking the upper extremity as an example, this study explores the potential of magnetic resonance microscopy (MRM) for the assessment of the development of the fetal upper extremity and discusses its correlation with histological findings.MethodsEx vivo MRM at 7.1 T (Clin Scan, Bruker Biospin, Germany) was performed in 10 human specimens at 8 to 12 weeks of gestational age (GA). In-plane resolution was 20 μm with a slice thickness of 70 μm. MRM was followed by histological work-up of the specimens. MRM images were then correlated with conventional histology with a focus on the presence of chondrification and ossification.ResultsOssification of the upper human extremity is detectable at 8 weeks GA in the humerus and the long bones of the forearm. There is excellent correlation for location and size of ossification between MRM and conventional histology. MRM imaging is in accordance with historical studies.ConclusionEx vivo MRM for the non-invasive assessment of the embryonic and fetal development of the upper human extremity is feasible. It may provide an accurate complementary tool for the evaluation of embryological development.