In vivo structural analysis of articular cartilage using diffusion tensor magnetic resonance imaging

Purpose

The articular cartilage is a small tissue with a matrix structure of three layers between which the orientation of collagen fiber differs. A diffusion-weighted twice-refocused spin-echo echo-planar imaging (SE-EPI) sequence was optimized for the articular cartilage, and the structure of the three layers of human articular cartilage was imaged in vivo from diffusion tensor images.

Materials and Methods

The subjects imaged were five specimens of swine femur head after removal of the flesh around the knee joint, five specimens of swine articular cartilage with flesh present and the knee cartilage of five adult male volunteers. Based on diffusion-weighted images in six directions, the mean diffusivity (MD) and the fractional anisotropy (FA) values were calculated.

Results

Diffusion tensor images of the articular cartilage were obtained by sequence optimization. The MD and FA value of the specimens (each of five examples) under different conditions were estimated. Although the articular cartilage is a small tissue, the matrix structure of each layer in the articular cartilage was obtained by SE-EPI sequence with GRAPPA. The MD and FA values of swine articular cartilage are different between the synovial fluid and saline. In human articular cartilage, the load of the body weight on the knee had an effect on the FA value of the surface layer of the articular cartilage.

Conclusion

This method can be used to create images of the articular cartilage structure, not only in vitro but also in vivo. Therefore, it is suggested that this method should support the elucidation of the in vivo structure and function of the knee joint and might be applied to clinical practice.     

In vivo imaging of blood flow in the mouse Achilles tendon using high-frequency ultrasound

Objective

Achilles tendinitis is a common clinical problem with many treatment modalities, including physical therapy, exercise and therapeutic ultrasound. However, evaluating the effects of current therapeutic modalities and studying the therapeutic mechanism(s) in vivo remains problematic. In this study, we attempted to observe the morphology and microcirculation changes in mouse Achilles tendons between pre- and post-treatment using high-frequency (25 MHz) ultrasound imaging. A secondary aim was to assess the potential of high-frequency ultrasound in exploring therapeutic mechanisms in small-animal models in vivo.

Methods

A collagenase-induced mouse model of Achilles tendinitis was adopted, and 5 min treatment of continuous-mode low-frequency (45 kHz) ultrasound with 47 mW/cm² maximum intensity and 16.3 cm² effective beam radiating area was applied. The B-mode images showed no focal hypoechoic regions in normal Achilles tendons either pre- or post-treatment. The Doppler power energy and blood flow rate were measured within the peritendinous space of the Achilles tendon.

Conclusion

An increase in the microcirculation was observed soon after the low-frequency ultrasound treatment, which was due to immediate induction of vascular dilatation. The results suggest that applying high-frequency Doppler imaging to small-animal models will be an invaluable aid in explorations of the therapeutic mechanism(s). Our future work includes using imaging to assess microcirculation changes in tendinitis between before and after treatment over a long time period, which is expected to yield useful physiological data for future human studies.     

In vivo nuclear magnetic resonance imaging and spectroscopy of aquatic organisms

NMR imaging and localized 1H spectroscopy of a variety of aquatic organisms in vivo is described for the first time. The practical consideration of life support, water volume, salinity, and anesthesia are discussed and solutions presented. Such animal studies shape our understanding of physiology, biochemistry, and biology, and provide models of human disease and normal function. These studies also have economic and ecological importance.     

In vivo detection of applied electric currents by magnetic resonance imaging

Magnetic resonance imaging is very sensitive to magnetic field variations. This inherent sensitivity can be exploited to measure small electric currents flowing in the human body. This report describes an experiment in which the magnetic fields produced by small currents applied to the forearm of a living subject have been detected in the tissue. It shows how such measurements have been used to measure current density. The suggested technique is used to measure one component of a current density in a saline solution in vitro.     

Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

In vivo tissue characterization by measurement of T1- and T2-relaxation processes is one of the greatest potentials of magnetic resonance imaging (MRI). This may be especially useful in the evaluation of bone marrow disorders as the MRI-signal from bone marrow is not influenced by the overlying osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the patients MRI was done at the time of diagnosis and during follow-up of chemotherapy and related to bone marrow biopsies taken within three days of the MRI. At the time of diagnosis T1-relaxation time was increased two to three times in the patients (range 0.7-3.0 sec.) compared to the controls (range 0.38-0.60 sec.). No significant difference was seen in the T2-relaxation process. In relation to chemotherapy T1 decreased towards the normal range in the patients who obtained complete remission, whereas T1 remained prolonged in the patients who did not respond successfully to the treatment. The results indicate that MRI may be a non-invasive clinically useful tool in the evaluation of acute leukaemia especially as a follow-up control of chemotherapy.     

In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging

Noninvasive cognitive neuroimaging studies based on functional magnetic resonance imaging (fMRI) are of ever-increasing importance for basic and clinical neurosciences. The explanatory power of fMRI could be greatly expanded, however, if the pattern of the neuronal circuitry underlying functional activation could be made visible in an equally noninvasive manner. In this study, blood oxygenation level-dependent (BOLD)-based fMRI and diffusion tensor imaging (DTI) were performed in the same cat visual cortex, and the foci of fMRI activation utilized as seeding points for 3D DTI fiber reconstruction algorithms, thus providing the map of the axonal circuitry underlying visual information processing. The methods developed in this study will lay the foundation for in vivo neuroanatomy and the ability for noninvasive longitudinal studies of brain development.     

In vivo multiparametric magnetic resonance imaging study for differentiating the severity of hepatic warm ischemia-reperfusion injury in a rabbit model

ObjectivesTo assess the value of multiparametric magnetic resonance imaging including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI in differentiating the severity of hepatic warm ischemia-reperfusion injury (WIRI) in a rabbit model.MethodsFifty rabbits were randomly divided into a sham-operation group and four test groups (n = 10 for each group) according to different hepatic warm ischemia times. IVIM, DTI and BOLD MRI were performed on a 3 T MR scanner with 11 b values (0 to 800 s/mm²), 2 b values (0 and 500 s/mm²) on 12 diffusion directions, multiple-echo gradient echo (GRE) sequences (TR/TE, 75/2.57–24.25 ms), respectively. IVIM, DTI and BOLD MRI parameters, hepatic biochemical and histopathological parameters were compared. Pearson and Spearman correlation methods were performed to assess the correlation between these MRI parameters and laboratory parameters. Furthermore, receiver operating characteristic (ROC) curves were compiled to determine diagnostic efficacies.ResultsTrue diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), mean diffusivity (MD) significantly decreased, while R2* significantly increased with prolonged warm ischemia times, and significant differences were found in all of biochemical and histopathological parameters (all P < 0.05). Dslow, PF, and R2* correlated significantly with all of biochemical and histopathological parameters (all |r| = 0.381–0.746, all P < 0.05). ROC analysis showed that the area under the ROC curve (AUC) of IVIM across hepatic WIRI groups was the largest among IVIM, DTI and BOLD.ConclusionsMultiparametric MRI may be helpful with characterization of early changes and determination of severity of hepatic WIRI in a rabbit model.     

In vivo fluorescent imaging of the mouse retina using adaptive optics

In vivo imaging of the mouse retina using visible and near infrared wavelengths does not achieve diffraction-limited resolution due to wavefront aberrations induced by the eye. Considering the pupil size and axial dimension of the eye, it is expected that unaberrated imaging of the retina would have a transverse resolution of 2 microm. Higher-order aberrations in retinal imaging of human can be compensated for by using adaptive optics. We demonstrate an adaptive optics system for in vivo imaging of fluorescent structures in the retina of a mouse, using a microelectromechanical system membrane mirror and a Shack-Hartmann wavefront sensor that detects fluorescent wavefront.     

Blood oxygenation level dependent magnetic resonance imaging and diffusion weighted MRI imaging for benign and malignant breast cancer discrimination

PurposeThe purpose of this study is to assess Blood oxygenation level dependent Magnetic Resonance Imaging (BOLD-MRI) and Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) in the differentiation of benign and malignant breast lesions.MethodsFifty-nine breast lesions (26 benign and 33 malignant lesions) pathologically proven in 59 patients were included in this retrospective study. As BOLD parameters were estimated basal signal S₀ and the relaxation rate R2*, diffusion and perfusion parameters were derived by DWI (pseudo-diffusion coefficient (Dp), perfusion fraction (fp) and tissue diffusivity (Dt)). Wilcoxon-Mann-Whitney U test and Receiver operating characteristic (ROC) analyses were calculated and area under ROC curve (AUC) was obtained. Moreover, pattern recognition approaches (linear discrimination analysis (LDA), support vector machine, k-nearest neighbours, decision tree) with least absolute shrinkage and selection operator (LASSO) method and leave one out cross validation approach were considered.ResultsA significant discrimination was obtained by the standard deviation value of S0, as BOLD parameter, that reached an AUC of 0.76 with a sensitivity of 65%, a specificity of 85% and an accuracy of 76%. No significant discrimination was obtained considering diffusion and perfusion parameters. Considering LASSO results, the features to use as predictors were all extracted parameters except that the mean value of R2* and the best result was obtained by a LDA that obtained an AUC = 0.83, with a sensitivity of 88%, a specificity of 77% and an accuracy of 83%.ConclusionsGood performance to discriminate benign and malignant lesions could be obtained using BOLD and DWI derived parameters with a LDA classification approach. However, these findings should be proven on larger and several dataset with different MR scanners.     

Blood oxygen level-dependent and perfusion magnetic resonance imaging: detecting differences in oxygen bioavailability and blood flow in transplanted kidneys

Functional magnetic resonance imaging (fMRI) is a powerful tool for examining kidney function, including organ blood flow and oxygen bioavailability. We have used contrast enhanced perfusion and blood oxygen level-dependent (BOLD) MRI to assess kidney transplants with normal function, acute tubular necrosis (ATN) and acute rejection. BOLD and MR-perfusion imaging were performed on 17 subjects with recently transplanted kidneys. There was a significant difference between medullary R2? values in the group with acute rejection (R2?=16.2/s) compared to allografts with ATN (R2?=19.8/s; P=.047) and normal-functioning allografts (R2?=24.3/s;P=.0003). There was a significant difference between medullary perfusion measurements in the group with acute rejection (124.4±41.1 ml/100 g per minute) compared to those in patients with ATN (246.9±123.5 ml/100 g per minute; P=.02) and normal-functioning allografts (220.8±95.8 ml/100 g per minute; P=.02). This study highlights the utility of combining perfusion and BOLD MRI to assess renal function. We have demonstrated a decrease in medullary R2? (decrease deoxyhemoglobin) on BOLD MRI and a decrease in medullary blood flow by MR perfusion imaging in those allografts with acute rejection, which indicates an increase in medullary oxygen bioavailability in allografts with rejection, despite a decrease in blood flow.     

Labeling of macrophages using bacterial magnetosomes and their characterization by magnetic resonance imaging

This work investigated macrophages labeled with magnetosomes for the possible detection of inflammations by MR molecular imaging. Pure magnetosomes and macrophages containing magnetosomes were analyzed using a clinical 1.5 T MR-scanner. Relaxivities of magnetosomes and relaxation rates of cells containing magnetosomes were determined. Peritonitis was induced in two mice. T₁, T₂ and T₂* weighted images were acquired following injection of the probes. Pure magnetosomes and labeled cells showed slight effects on T₁, but strong effects on T₂ and T₂* images. Labeled macrophages were located with magnetic resonance imaging (MRI) in the colon area, thus demonstrating the feasibility of the proposed approach.     

In vivo photoacoustic chorioretinal vascular imaging in albino mouse

Photoacoustic ophthalmoscopy(PAOM) is a novel imaging modality, which is capable of non-invasively detecting optical absorption properties in the retina. We visualize the microvasculature in retina and choroid in albino mouse using PAOM guided by spectral-domain optical coherence tomography. Since albino mouse characterizes by lacking melanin in retinal pigment epithelium(RPE), PAOM illumination laser can penetrate through the RPE onto choroid, and consequently provides volumetric visualization of chorioretinal vasculatures as a result of strong hemoglobin optical absorption. The high-quality chorioretinal microvascular imaging acquired by PAOM implies its great potential in understanding pathological mechanisms and developing therapeutic strategies for major chorioretinal diseases that correlate with vascular disorders.     

Detection of a systemic effect of malignancy in vivo by magnetic resonance imaging

In animals bearing tumors prolongation of spin lattice relaxation time (T1) has been detected in vitro in organs not directly affected by the malignancy. This has been termed the "Systemic Effect." In this study the possible existence of such an effect in the liver, muscle and fat of humans with lymphoma has been investigated. In vivo T1 measurements were made using a low field strength (0.08 Tesla) magnetic resonance imager. The mean liver T1 for 19 lymphoma patients with normal liver histology was 206 ms, compared with a mean of 191 ms for 61 volunteers (p less than 0.0001). Among these patients prolongation of liver T1 was related to the extent of disease elsewhere in the body. For 23 patients with Hodgkin's disease (HD) examined at the time of diagnosis, liver T1 was significantly correlated with other known markers of disease extent or activity (alkaline phosphatase level, erythrocyte sedimentation rate and the presence of systemic symptoms). No such correlations were observed among 25 patients with non-Hodgkin's lymphoma (NHL). Muscle and fat T1 was measured in 26 patients with lymphoma, 14 patients with acute leukemia and 88 volunteers. Seven of the patients with lymphoma and 2 of those with leukemia had muscle T1 values above the range observed for volunteers. Similarly, 3 patients with lymphoma and 1 with leukemia had prolonged fat T1. These findings indicate that a systemic effect of malignancy on T1 is detectable in a proportion of humans with lymphoma or leukemia.     

In vivo sodium-23 magnetic resonance surface coil imaging: Observing experimental cerebral ischemia in the rat

Sodium-23 magnetic resonance imaging can be used to detect and assess experimental cerebral ischemia in the rat. An imaging technique utilizing a surface coil is described to produce sodium magnetic resonance images of good quality and resolution within 10 min. A novel method of hemispheric occlusion showed edema in the right brain of the rat head within 3 hr after injury. The edema was especially pronounced by 12 hr with effects in the right brain, eye and surrounding muscle evident.     

Multi-dimensional magnetic resonance imaging in a stray magnetic field

Stray field imaging has been extensively utilized in the last 10 years to perform very high resolution imaging of samples in a single dimension using the massive field gradient present in the fringe of a superconducting magnet. By spinning the sample around the magic-angle, the stray field gradient is successively reoriented along three orthogonal directions in the sample reference frame, allowing the acquisition of a full three-dimensional Fourier image, thereby providing the possibility to perform multi-dimensional very high-resolution imaging with standard nuclear magnetic resonance spectroscopy equipment. Here, we show multi-dimensional images demonstrating the feasibility of this technique.     

High-resolution magnetic resonance flow imaging in a model of porous bone-implant interface

PURPOSE: To evaluate the application of high-resolution MRI methodology for characterizing the fluid velocity field and evaluate fluid shear field within a simplified in vitro model of a bone-implant interface. MATERIALS AND METHODS: The study used a specific micromotion canine bone implant that has been used for over a decade in the experimental evaluation of anatomical, biomaterial, mechanical and surgical factors influencing the quality of the implant interface. To allow its implementation in an MR coil, a nonmagnetic model of the micromotion implant was fabricated. The model consisted of a cylinder of polymethylmethacrylate (PMMA) representing the implant, located within an annular controlled gap into a block of coralline-derived bulk porous hydroxyapatite (HA; Interpore Cross International, Irvine, CA, USA). The assembly was potted in a polycarbonate shell and connected to a gravity-feed flow system consisting of a water fluid reservoir and peristaltic pump. Cross-sectional fluid velocity images through the principal axis of the implant were generated using a phase-encoding MR imaging technique; axial fluid flow was derived, and fluid shear was evaluated using a Newtonian fluid model. RESULTS: Due to the nonuniform gap of the actual experimental construct, a highly nonuniform flow through the annular gap and a secondary flow through the porous HA block were observed. Axial velocity magnitudes in the range 0.04 to 14 mm/s were measured, and the flow velocities within the annular gap and the surrounding bone differed by nearly two orders of magnitude. Image analysis showed that 95% of total flow passed through the annular gap and 5% was transported through the porous HA block. Fluid shear was computed within the porous structure and the annular gap, and they differed by one order of magnitude. CONCLUSION: We demonstrated that high-resolution MR flow imaging has the resolution to measure fluid transport processes noninvasively through a nonmagnetic model bone implant. Gap fluid flow and fluid flow into the permeable skeleton (HA block) were quantified, and these data allowed the noninvasive determination of fluid shear. These promising results are encouraging for applications in biological tissue, artificial bone substitutes, tissue engineering and clinically relevant studies concerning implant fixation.