Quantifying the volume fraction and texture of cancellous bone using 3.0 Tesla magnetic resonance imaging

Introduction: 3.0 Tesla MRI offers the potential to quantify the volume fraction and structural texture of cancellous bone, along with quantification of marrow composition, in a single non-invasive examination. This study describes our preliminary investigations to identify parameters which describe cancellous bone structure including the relationships between texture and volume fraction.

Magnetic resonance spectroscopy in seizure disorders

Key points • The clinical aims of MR spectroscopy (MRS) in seizure disorders are to help identify, localize and characterize epileptogenic foci. • Lateralizing MRS abnormalities in temporal lobe epilepsy (TLE) may be used clinically in combination with structural and T2 MRI measurements together with other techniques such as EEG, PET and SPECT. • Characteristic metabolite abnormalities are decreased N-acetylaspartate (NAA) with increased choline (Cho) and myoinositol (mI) (short-echo time). • Contralateral metabolite abnormalities are frequently seen in TLE, but are of uncertain significance. • In extra-temporal epilepsy, metabolite abnormalities may be seen where MR imaging (MRI) is normal; but may not be sufficiently localized to be useful clinically. • MRS may help to characterize epileptogenic lesions visible on MRI (aggressive vs. indolent neoplastic, dysplasia). • Spectral editing techniques are required to evaluate specific epilepsy-relevant metabolites (e.g. -aminobutyric acid (GABA)), which may be useful in drug development and evaluation. • MRS with phosphorus (31P) and other nuclei probe metabolism of epilepsy, but are less useful clinically. • There is potential for assessing the of drug mode of action and efficacy through 13C carbon metabolite measurements, while changes in sodium homeostasis resulting from seizure activity may be detected with 23Na MRS.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN: Observational, before and after CPAP treatment. SETTING: Two tertiary hospital research institutes. PARTICIPANTS: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia. CITATION: O'Donoghue FJ; Wellard RM; Rochford PD; Dawson A; Barnes M; Ruehland WR; Jackson ML; Howard ME; Pierce RJ; Jackson GD. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.

3D reconstruction of long bones utilising magnetic resonance imaging (MRI)

The design of pre-contoured fracture fixation implants (plates and nails) that correctly fit the anatomy of a patient utilises 3D models of long bones with accurate geometric representation. 3D data is usually available from computed tomography (CT) scans of human cadavers that generally represent the above 60 year old age group. Thus, despite the fact that half of the seriously injured population comes from the 30 year age group and below, virtually no data exists from these younger age groups to inform the design of implants that optimally fit patients from these groups. Hence, relevant bone data from these age groups is required. The current gold standard for acquiring such data–CT–involves ionising radiation and cannot be used to scan healthy human volunteers. Magnetic resonance imaging (MRI) has been shown to be a potential alternative in the previous studies conducted using small bones (tarsal bones) and parts of the long bones. However, in order to use MRI effectively for 3D reconstruction of human long bones, further validations using long bones and appropriate reference standards are required. Accurate reconstruction of 3D models from CT or MRI data sets requires an accurate image segmentation method. Currently available sophisticated segmentation methods involve complex programming and mathematics that researchers are not trained to perform. Therefore, an accurate but relatively simple segmentation method is required for segmentation of CT and MRI data. Furthermore, some of the limitations of 1.5T MRI such as very long scanning times and poor contrast in articular regions can potentially be reduced by using higher field 3T MRI imaging. However, a quantification of the signal to noise ratio (SNR) gain at the bone - soft tissue interface should be performed; this is not reported in the literature. As MRI scanning of long bones has very long scanning times, the acquired images are more prone to motion artefacts due to random movements of the subject‟s limbs. One of the artefacts observed is the step artefact that is believed to occur from the random movements of the volunteer during a scan. This needs to be corrected before the models can be used for implant design. As the first aim, this study investigated two segmentation methods: intensity thresholding and Canny edge detection as accurate but simple segmentation methods for segmentation of MRI and CT data. The second aim was to investigate the usability of MRI as a radiation free imaging alternative to CT for reconstruction of 3D models of long bones. The third aim was to use 3T MRI to improve the poor contrast in articular regions and long scanning times of current MRI. The fourth and final aim was to minimise the step artefact using 3D modelling techniques. The segmentation methods were investigated using CT scans of five ovine femora. The single level thresholding was performed using a visually selected threshold level to segment the complete femur. For multilevel thresholding, multiple threshold levels calculated from the threshold selection method were used for the proximal, diaphyseal and distal regions of the femur. Canny edge detection was used by delineating the outer and inner contour of 2D images and then combining them to generate the 3D model. Models generated from these methods were compared to the reference standard generated using the mechanical contact scans of the denuded bone. The second aim was achieved using CT and MRI scans of five ovine femora and segmenting them using the multilevel threshold method. A surface geometric comparison was conducted between CT based, MRI based and reference models. To quantitatively compare the 1.5T images to the 3T MRI images, the right lower limbs of five healthy volunteers were scanned using scanners from the same manufacturer. The images obtained using the identical protocols were compared by means of SNR and contrast to noise ratio (CNR) of muscle, bone marrow and bone. In order to correct the step artefact in the final 3D models, the step was simulated in five ovine femora scanned with a 3T MRI scanner. The step was corrected using the iterative closest point (ICP) algorithm based aligning method. The present study demonstrated that the multi-threshold approach in combination with the threshold selection method can generate 3D models from long bones with an average deviation of 0.18 mm. The same was 0.24 mm of the single threshold method. There was a significant statistical difference between the accuracy of models generated by the two methods. In comparison, the Canny edge detection method generated average deviation of 0.20 mm. MRI based models exhibited 0.23 mm average deviation in comparison to the 0.18 mm average deviation of CT based models. The differences were not statistically significant. 3T MRI improved the contrast in the bone–muscle interfaces of most anatomical regions of femora and tibiae, potentially improving the inaccuracies conferred by poor contrast of the articular regions. Using the robust ICP algorithm to align the 3D surfaces, the step artefact that occurred by the volunteer moving the leg was corrected, generating errors of 0.32 ± 0.02 mm when compared with the reference standard. The study concludes that magnetic resonance imaging, together with simple multilevel thresholding segmentation, is able to produce 3D models of long bones with accurate geometric representations. The method is, therefore, a potential alternative to the current gold standard CT imaging.

In vitro estimation of foetal liver volume using ultrasound, x-ray computed tomography and magnetic resonance imaging

Sixteen formalin-fixed foetal livers were scanned in vitro using a new system for estimating volume from a sequence of multiplanar 2D ultrasound images. Three different scan techniques were used (radial, parallel and slanted) and four volume estimation algorithms (ellipsoid, planimetry, tetrahedral and ray tracing). Actual liver volumes were measured by water displacement. Twelve of the sixteen livers also received x-ray computed tomography (CT) and magnetic resonance (MR) scans and the volumes were calculated using voxel counting and planimetry. The percentage accuracy (mean ± SD) was 5.3 ± 4.7%, −3.1 ± 9.6% and −0.03 ± 9.7% for ultrasound (radial scans, ray volumes), MR and CT (voxel counting) respectively. The new system may be useful for accurately estimating foetal liver volume in utero.

Microstructural magnetic resonance imaging of articular cartilage

The focus of this Editorial is recent developments in magnetic resonance imaging (MRI) modalities for evaluation of the microstructure and macromolecular organisation of articular cartilage. We place a specific emphasis on three types of measurements: (1) MRI transverse spin-relaxation mapping (T2 mapping); (2) diffusion-tensor imaging; and (3) compression micro-MRI (uMRI) measurements of articular cartilage in vitro. Such studies have a significant role to play in improving the understanding of the fundamental biomechanics of articular cartilage and in the development of in vitro models of early osteoarthritis. We discuss how the supramolecular organisation of the cartilage extracellular matrix and its behaviour under mechanical compression can be inferred from diffusion-tensor and T2 maps with in-plane resolution ~100 um. The emphasis is on in vitro studies performed under controlled physiological conditions but in vivo applications of T2 mapping and DTI are also briefly discussed.

Ventilation distribution in rats : part 2 – a comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

Background: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. Methods: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. Results: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. Conclusion: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.

Biomechanics of synthetic elastin : insights from Magnetic Resonance microimaging

We used Magnetic Resonance microimaging (μMRI) to study the compressive behaviour of synthetic elastin. Compression-induced changes in the elastin sample were quantified using longitudinal and transverse spin relaxation rates (R1 and R2, respectively). Spatially-resolved maps of each spin relaxation rate were obtained, allowing the heterogeneous texture of the sample to be observed with and without compression. Compression resulted in an increase of both the mean R1 and the mean R2, but most of this increase was due to sub-locations that exhibited relatively low R1 and R2 in the uncompressed state. This behaviour can be described by differential compression, where local domains in the hydrogel with a relatively low biopolymer content compress more than those with a relatively high biopolymer content.

A study of the diffusion characteristics of normal, delipidized and relipidized articular cartilage using magnetic resonance imaging

This paper assesses the capacity to provide semipermeability of the synthetic layer of surface-active phospholipids created to replace the depleted surface amorphous layer of articular cartilage. The surfaces of articular cartilage specimens in normal, delipidized, and relipidized conditions following incubation in dipalmitoyl-phosphatidylcholine and palmitoyl-oleoyl-phosphatidylcholine components of the joint lipid mixture were characterized nanoscopically with the atomic force microscope and also imaged as deuterium oxide (D2O) diffused transiently through these surfaces in a magnetic resonance imaging enclosure. The MR images were then used to determine the apparent diffusion coefficients in a purpose-built MATLAB®-based algorithm. Our results revealed that all surfaces were permeable to D2O, but that there was a significant difference in the semipermeability of the surfaces under the different conditions, relative to the apparent diffusion coefficients. Based on the results and observations, it can be concluded that the synthetic lipid that is deposited to replace the depleted SAL of articular cartilage is capable of inducing some level of semipermeability.

Diffusion-sensitive magnetic resonance spectroscopy and imaging in biomedical sciences

We present a mini-review of the development and contemporary applications of diffusion-sensitive nuclear magnetic resonance (NMR) techniques in biomedical sciences. Molecular diffusion is a fundamental physical phenomenon present in all biological systems. Due to the connection between experimentally measured diffusion metrics and the microscopic environment sensed by the diffusing molecules, diffusion measurements can be used for characterisation of molecular size, molecular binding and association, and the morphology of biological tissues. The emergence of magnetic resonance was instrumental to the development of biomedical applications of diffusion. We discuss the fundamental physical principles of diffusion NMR spectroscopy and diffusion MR imaging. The emphasis is placed on conceptual understanding, historical evolution and practical applications rather than complex technical details. Mathematical description of diffusion is presented to the extent that it is required for the basic understanding of the concepts. We present a wide range of spectroscopic and imaging applications of diffusion magnetic resonance, including colloidal drug delivery vehicles; protein association; characterisation of cell morphology; neural fibre tractography; cardiac imaging; and the imaging of load-bearing connective tissues. This paper is intended as an accessible introduction into the exciting and growing field of diffusion magnetic resonance.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.