Articular cartilage volume in the knee: semiautomated determination from three-dimensional reformations of MR images

PURPOSE: To determine the accuracy of semiautomated quantification of articular cartilage volume from three-dimensional (3D) reformations of magnetic resonance (MR) images. MATERIALS AND METHODS: Sagittal, fat-suppressed, 3D, spoiled gradient-recalled-echo MR imaging of two bovine and two human cadaver knees was performed. Articular cartilage volume was calculated from 3D reformations of the MR images by using a semiautomated program written at the authors' institution. Calculated volumes were compared with directly measured volumes of the surgically removed articular cartilage. RESULTS: The percentage of error of the MR imaging-determined volumes was 6.53% +/- 4.75 (mean +/- standard deviation). A strong correlation between the two sets of observations was shown (r=.997). Linear regression showed the calculated volumes to be highly accurate (slope=1.002, P>.25). Repeated reformations yielded volumes that were reproducible (mean absolute error, 0.013 mL +/- 0.019) and not significantly different from the measured volume (P>.10). CONCLUSION: Semiautomated quantification of knee articular cartilage from MR images yields highly accurate cartilage volumes.     

Measurement of synovial lining volume by magnetic resonance imaging of the knee in chronic synovitis

OBJECTIVES: Current methods of monitoring chronic synovitis in a single joint rely on clinical examination derived indices, such as the detection of synovial thickening. This study aimed to develop a reproducible method for quantifying the volume of synovial lining in chronic synovitis using contrast enhanced magnetic resonance (MR) imaging. METHODS: The knees of 18 patients with chronic synovitis were examined (34 studies). A 2D T1 weighted FLASH sequence was used to evaluate the temporal enhancement of synovial structures after intravenous contrast. Synovial lining volume was calculated from subtraction of pre and post-enhancement 3D T1 weighted MP RAGE images with thresholding and pixel counting. Eleven patients were examined before and after intra-articular glucocorticoid (mean interval 14 weeks) and MR data compared with changes in clinical examination derived indices of disease activity. RESULTS: Synovial lining volume varied from 52-267 ml. The coefficient of variation in volume calculation was 3.5% for a single observer and was 3.8% for two observers. Synovial lining volume was quantified in all patients where synovial lining thickening could not be detected clinically. A decrease in synovial lining volume of > 40% was associated with an improvement in synovial lining thickening, detected clinically. Decreases in synovial lining volume were quantified by MR in two of three patients where changes in clinical examination derived indices were inconsistent. CONCLUSIONS: A reproducible method of estimating the volume of synovial lining in patients with chronic synovitis has been developed. MR measurement of synovial lining volume may quantify changes in chronic synovitis that remain unidentified by clinical measures.     

Quantitation of 5-fluorouracil catabolism in human liver in vivo by three-dimensional localized 19F magnetic resonance spectroscopy

The development of clinical applications of 19F magnetic resonance (MR) spectroscopy of 5-fluorouracil (5-FU) has been limited by the inability to localize 19F spectra to specific regions of interest, making it difficult to quantitate drug and metabolite concentrations accurately. To develop methodology for quantitation, we studied the liver of patients receiving rapid bolus i.v. injections of 5-FU. In serial studies, 5-FU disappeared from the liver within 17-26 min, and its catabolite, alpha-fluoro-beta-alanine (FBAL), rose to reach a plateau after 40 min. A high peak level of fluoro-ureido-propionic acid preceded that of FBAL in only one patient, and dihydrofluorouracil was never observed. During the plateau, we obtained MR imaging-directed 19F MR spectra localized using three-dimensional chemical shift imaging. The spin-lattice relaxation time of FBAL in liver, measured using a variable nutation angle method, was 1.6 +/- 0.2 s (mean +/- SD; n = 5). The concentration of FBAL at 60 +/- 10 min after injection was 1.0 +/- 0.2 mm in liver (mean +/- SD; n = 7). This amount represents approximately 20% of the injected dose and 1.4 times the initial hepatic 5-FU concentration. Our approach may permit one to obtain molar concentrations of fluoropyrimidine metabolites simultaneously in hepatic cancers and surrounding liver, and it helps expand pharmacokinetic modeling of fluoropyrimidine catabolism.     

Three-dimensional thickness and volume measurements of the knee joint cartilage by MR tomography: reproducibility in volunteers]

A rapidly expanding number of genetic mechanisms contributing to disease can be accessed via molecular analysis. In order to take full advantage of this potential for genetic diagnostics, and to monitor treatment by gene therapy and other emerging methods, a new generation of diagnostic techniques will be required. Of central importance in future analyses is the possibility to perform very large numbers of simultaneous genetic analyses in analytical devices of small linear dimensions. We have developed a new molecular probe design that is amenable to highly multiplex, specific analyses of total genomic DNA or of RNA molecules expressed in tissue samples. Here, a brief history of gene analytical procedures is presented, followed by a discussion of the properties, means of synthesis and applications of this new class of gene analytic reagents, padlock probes.     

Multidimensional wavelet analysis of functional magnetic resonance images

We have found that copper(II) compounds containing a peptide group in the chelate exhibit high activity for modification or degradation of albumin in the presence of hydrogen peroxide, whereas no activity was detected for the copper(II) compounds without an amide-group. It is suggested that presence of the amide-group in the ligand may play an important role in the formation of a peroxide adduct and in activation of the peroxide ion, leading to cleavage of the peptide bond of a neighboring protein. It is implied that conversion of normal cellular prion protein PrPC into a disease-causing isoform, PrPSc is attributed to the activated peroxide ion coordinated to a copper(II) captured in the NH2-terminal domain of the PrPC.     

Sex-specific analysis of cartilage volume in the knee joint--a quantitative MRI-based study

Thrombospondin-1 (TSP-1), an adhesive glycoprotein, plays an important role in platelet adhesion, inflammation, cell-to-cell interaction, and angiogenesis. TSP-1 is expressed by endothelial cells, fibroblasts, and macrophages. TSP-1's unique cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) specific receptor plays an important role in the binding and modulation of cellular adhesion and invasion. This article histologically and quantitatively evaluates TSP-1 and its CSVTCG receptor in adult burn wounds over time. Tissue was obtained from burn wounds on several days and samples that were 5 microns thick were placed on slides. Expression of TSP-1 and its CSVTCG receptor were evaluated immunohistochemically and quantitated by computer image analysis in units of absorbance. Immunoglobin G (IgG) (negative) controls were performed and subtracted from the TSP-1 sample to eliminate background absorbance readings. Serum (negative) control was used for the CSVTCG receptor. Platelet concentrates were used as the positive control. A quantitative examination of the results yielded the following information, expressed as absorbance +/- standard error of the mean: TSP-1: day 1, 62.0 +/- 10.13; day 3, 76.2 +/- 6.90; day 5, 36.0 +/- 3.96; day 7, 60.4 +/- 5.67; and day 9, 29.5 +/- 2.91. TSP-1 displays an early peak, followed by a steep decrease over the time period studied. The readings for the CSVTCG receptor are as follows: day 1, 33.8 +/- 1.87; day 3, 34.5 +/- 5.39; day 7, 39.1 +/- 1.93; day 21, 39.1 +/- 1.93; day 28, 34.8 +/- 3.67. In contrast, the CVSTCG receptor continues to be present in the wound over time. Histologic findings are reported, and photographs and a histopathologic analysis are included. The information presented in this article leads to the conclusion that temporal and histologic differences exist in the localization and expression of TSP-1 and its CSVTCG receptor. TSP-1 is up-regulated in injured tissues immediately after the injury; it is rapidly down-regulated as the tissue heals. In contrast, the levels of the CSVTCG receptor remain relatively constant during the healing process. These data are consistent with TSP-1's known role in cell-to-cell interaction, including the modulation of the growth factor and protease activity.     

Repeatability of patellar cartilage thickness patterns in the living, using a fat-suppressed magnetic resonance imaging sequence with short acquisition time and three-dimensional data processing

Twenty-two patients with large nonossifying fibromas (NOFs) in weight-bearing bones were studied to evaluate risk of pathologic fracture. Previous reports suggest an absolute size threshold for NOFs beyond which there is a reasonable chance of impending fracture. In this series, 13 (59%) large NOFs had not had pathologic fracture despite exceeding the previously established size threshold. Four of the patients had fractures of the long bone in which the NOF was located without the fracture involving the lesion. In the nine (41%) patients in whom pathologic fracture occurred, healing was uneventful after closed reduction and cast immobilization. Whereas absolute size parameters may be useful in predicting pathologic fracture rate, they do not imply a requirement for prophylactic curettage and bone grafting. The majority of patients with large NOFs can be monitored without surgical intervention, and fractures can be successfully managed with nonoperative treatment.     

An ellipsoidal shell model for volume estimation of the right ventricle from magnetic resonance images

RATIONALE AND OBJECTIVES: I developed a volume estimation technique for the crescentic volume of the right ventricle (RV) of the heart. A geometric model was desired to avoid the lengthy data collection and reduction required by Simpson's rule. METHODS: An ellipsoidal shell model was developed that requires only simple mathematics and that resembles the RV shape. RV cast volumes were obtained by water displacement and Simpson's rule and model-based calculations using magnetic resonance (MR) imaging. RESULTS: Model-based estimates correlated well with water displacement volumes (r = 0.924), with a slope not significantly different from unity. Simpson's rule results showed a higher correlation (r = 0.994), but it required longer acquisition and processing. Geometric irregularity in the RV shape required no modification in mathematics. CONCLUSION: The model provides reliable RV volume estimates from two MR image planes. The mathematics provides a simple approach to a relatively complex, crescentic shape. Short times for data acquisition and analysis suggest the potential for time savings during routine clinical measurements.     

The human brain age 7-11 years: a volumetric analysis based on magnetic resonance images

Volumetric magnetic resonance image (MRI)-based morphometry was performed on the brains of 30 normal children (15 males and 15 males) with a mean age of 9 years (range 7-11 years). This age range lies in a late but critical phase of brain growth where not volumetric increment will be small but when the details of brain circuity are being fine-tuned to support the operations of the adult brain. The brain at this age is 95% the volume of the adult brain. The brain of the female child is 93% the volume of the male child. For more than 95% of brain structures, the volumetric differences in male and female child brain are uniformly scaled to the volume difference of the total brain in the two sexes. Exceptions to this pattern of uniform scaling are the caudate, hippocampus and pallidum, which are disproportionately larger in female than male child brain, and the amygdala, which is disproportionately smaller in the female child brain. The patterns of uniform scaling are generally sustained during the final volumetric increment in overall brain size between age 7-11 and adulthood. There are exceptions to this uniform scaling of child to adult brain, and certain of these exceptions are sexually dimorphic. Thus, with respect to major brain regions, the cerebellum in the female but not the male child is already at adult volume while the brainstem in both sexes must enlarge more than the brain as a whole. The collective subcortical gray matter structures of the forebrain of the female child are already at their adult volumes. The volumes of these same structures in the male child, by contrast, are greater than their adult volumes and, by implication, must regress in volume before adulthood. The volume of the central white matter, on the other hand, is disproportionately smaller in female than male child brain with respect to the adult volumes of cerebral central white matter. By implication, relative volumetric increase of cerebral central white matter by adulthood must be greater in the female than male brain. The juxtaposed progressive and regressive patterns of growth of brain structures implied by these observations in the human brain have a soundly established precedent in the developing rhesus brain. There is emerging evidence that sexually dimorphic abnormal regulation of these terminal patterns of brain development are associated with gravely disabling human disorders of obscure etiology.     

Visualization of inner ear structures by three-dimensional high-resolution magnetic resonance imaging

High-resolution computed tomography (CT) has long been the method of choice in the visualization of the petrous bone, the internal auditory canal, and the cerebellopontine angle. The introduction of magnetic resonance imaging (MRI), especially of the three-dimensional Fourier transformation constructive interference in steady state (3DFT-CISS), has proved to be superior in the detection of soft-tissue lesions in the inner ear. The aim of this study was to visualize small anatomic structures of the inner ear and cerebellopontine angle. The examinations were performed with a standard head coil on a 1.5-T Magnetom ("Vision"; Siemens, Erlangen, Germany). The three-dimensional reconstruction of the cochlea, semicircular canals, and vestibulum allowed detailed visualization, as well as the imaging of cranial nerves VII and VIII. Our results indicate that 3DFT-CISS MRI is a valuable diagnostic tool in the evaluation of inner ear anatomy and pathology; in most cases, however, it must be supplemented by HR-CT.     

Functionality and connectivity analysis by magnetic resonance imaging

Magnetic resonance (MR is a remarkably versatile technology applicable to various aspects of medical science. Currently, there are three categories of MR techniques available for probing human brain function in detail. The first category comprises the most widely utilized techniques which make use of the metabolic effects of brain activation, represented by BOLD (blood oxygenation level dependent) functional magnetic resonance imaging (fMRI). The second category of techniques deals with apparent diffusion tensor probing the axonal connectivity and is represented by three dimensional anisotropy contrast (3DAC) axonography. The third category of techniques is a biological application of classical nuclear magnetic resonance (NMR) spectroscopy capable of providing biochemical information in vivo and is represented by spectroscopic imaging (SI). As techniques directly applicable to clinical medicine, BOLD fMRI and 3DAC axonography possess the highest potential.     

Reproducibility of fat area measurements in young, non-obese subjects by computerized analysis of magnetic resonance images

OBJECTIVE: To assess reproducibility, expressed as both inter-observer variability and intra-observer variability, of fat area measurements on images obtained by magnetic resonance (MR); to compare variability between fat area measurements, calculated from a single image per body region and from the average fat area of three images, and to determine reproducibility of image acquisition at the abdominal level. SUBJECTS: Thirty young, non-obese subjects (reproducibility of image analysis) and nine young, non-obese subjects (reproducibility of image acquisition). METHODS: Three MR images at the level of the abdomen (in 30 subjects) and at the level of the hip and thigh (in 14 of them). Quantification of subcutaneous fat depots (abdomen, hip and thigh) and visceral fat depots using an image-analyzing computer program. Assessment of variability of image analysis for fat area measurements between two observers and within observers. Assessment of reproducibility of image acquisition at the abdominal level (in nine subjects). RESULTS: Subcutaneous fat areas in all body regions were quantified with coefficients of variation (CV) ranging from only 2.1%-4.9%. By contrast, visceral fat area measurements showed markedly higher CVs (range: 9.4%-17.6%). Moreover, relative variability was much larger in small visceral fat areas (CVs up to 25.6%). The majority of CVs, calculated for intra-observer variability and calculated from the average fat area measurements of three images, was lower than calculated for inter-observer variability and for one single image, respectively. In particular, for the visceral fat depot, this reduction in variability had practical consequences for the number of subjects required for a study. Variation of repeated image acquisition was in the same range as variation of repeated measurements on the same image. CONCLUSION: One image per body site is sufficient to obtain a reliable estimate of subcutaneous fat depots. For estimations of the visceral fat depot, the average area measurements of three images reduces variability and increases statistical power. The availability of one single experienced observer during a study adds to accuracy.     

Conformational analysis of potent sweet taste ligands by nuclear magnetic resonance, computer simulations and X-ray diffraction studies

Four potent sweet-tasting molecules, N-(3,3-dimethylbutyl)-L-aspartyl-L-phenylalanine methylester 1 (7000 times more potent than sucrose), N-(3,3-dimethylbutyl)-L-aspartyl-D-valine (S)-alpha-ethylbenzylamide 2 (3000 time more potent than sucrose), L-aspartyl-D-valine (R)-alpha-methoxymethylbenzylamide 3 (1350 times more potent than sucrose and L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide 4 (2500 times more potent than sucrose) were studied by 1H NMR and computer simulations. These flexible molecules adopt multiple conformations in solution. The "L-shaped" structure, which we believe to be responsible for sweet taste is accessible to all four compounds in solution. Extended conformations with the AH and B-containing moieties in the +y-axis and the hydrophobic group X pointing in the y-axis have also been observed for all four sweeteners. For compounds 1 and 3, the solid-state conformations were determined by X-ray diffraction studies. These results demonstrate that compounds 1 and 3 adopt an "L-shaped" structure even in the crystalline state. The extraordinary potency of the N-alkylated compound 1 compared with the unsubstituted Asp-Phe-OMe may be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the "L-shaped" structure.     

Quantitative analysis of incongruity, contact areas and cartilage thickness in the human hip joint

Joint incongruity and cartilage thickness have been shown to determine the contact stresses and the load partitioning between the solid and fluid phases of articular cartilage. Matrix stresses, which are relevant in the development of osteoarthrosis, can, however, not be determined experimentally but must be calculated using numerical methods. The aim of the present study was to quantify the incongruity and cartilage thickness of the human hip, in order to allow for the construction of morphologically accurate finite element models. Twelve cadaveric specimens (34-86 years), two fresh and ten fixed, were investigated. The loading configuration was based on in vivo measurements of hip joint forces during midstance. The incongruity and contact areas were determined using a polyether casting technique, in the minimally and the fully loaded state. The cartilage thickness was measured at identical coordinate points with an A-mode ultrasonic system. Generally, the contact started at lower loads at the edge of the lunate surface, and the joint space increased towards its central aspects. In some specimens the contact started in the acetabular roof, leaving a joint space of up to 2 mm in the horns of the lunate surface. In others, the initial contact was observed in the anterior and posterior horns of the lunate surface with a joint space width of up to 0.75 mm in the acetabular roof. The size of the contact areas increased from about 20% of the lunate surface to 98% at higher loads. The articular cartilage thickness ranged from 0.7 to 3.6 mm, the maxima being located in the ventral aspects of the femoral head and acetabulum. These quantitative data on joint space width, contact, and cartilage thickness in the human hip joint may be used to construct and validate finite element models which are required to elucidate the mechanical factors involved in osteoarthrosis.     

Multivariate image analysis of magnetic resonance images with the direct exponential curve resolution algorithm (DECRA). Part 2: Application to human brain images

Seasonal levels of cortisol, growth hormone (GH), insulin like growth factor 1 (IGF-1), glucose, triiodothyronine (T3), free T3, thyroxine and free fatty acids (FFA) were measured every 3 weeks for 54 weeks in the plasma of five adult bulls, and four barren and five pregnant Alaskan reindeer (Rangifer tarandus) cows. Three consecutive samples were taken from each animal. Cortisol levels exhibited wide seasonal variation (9-45 ng/ml) [corrected] without any peak or difference in levels among groups. Rising levels were detected between the 3 consequent samples. Peak GH levels, detected during January and February, were higher in the non-pregnant group (54 ng/ml) than the pregnant (26 ng ml-1) and the male (27 ng ml-1) groups. Low GH levels (2-10 ng ml-1) were recorded between May and September. IGF-1 reached peak levels (715 ng ml-1) in males in August, in non-pregnant females in September (677 ng ml-1), and in the pregnant females in October (505 ng ml-1). Seasonal minima (404 in males, 172 and 93 in pregnant and non-pregnant groups) were detected in February. Glucose was fairly stable throughout the year (100-200 mg/100 ml). A rising levels were found between the three consecutive samples. Triiodothyronine (T3) (2.16-2.30 ng ml-1) peaked in all three groups during the spring and early summer, and minimal levels (0.61-0.97 ng ml-1) were detected from October to January. Conversely, thyroxine or free T3 did not exhibit seasonal variation. FFA fluctuated widely (97-1076 nmol l-1) throughout the year. Only in pregnant females were concentrations more stable (150-460 nmol l-1). Perhaps, because of ad libitum supply of food in captive reindeer, only T3 and GH exhibited pronounced seasonal fluctuations which could be related to the metabolic changes expected during the annual cycle.     

Paraplane analysis from precordial three-dimensional echocardiographic data sets for rapid and accurate quantification of left ventricular volume and function: a comparison with magnetic resonance imaging

OBJECTIVES: Three-dimensional echocardiography (3DE) calculates left ventricular volumes (LVV) and ejection fraction (EF) without geometric assumptions, but prolonged analysis time limits its routine use. This study was designed to validate a modified 3DE method for rapid and accurate LVV and EF calculation compared with magnetic resonance imaging (MRI). METHODS: Forty subjects included 15 normal volunteers (group A) and 25 patients with segmental wall motion abnormalities and global hypokinesis caused by ischemic heart disease (group B) who underwent 3DE with precordial rotational acquisition technique (2-degree interval with electrocardiographic and respiratory gating) and MRI at 0.5 T, electrocardiogram (ECG)-triggered multislice multiphase T1-weighted fast field echo. End-diastolic and end-systolic LVV and EF were calculated from both techniques with Simpson's rule by manual endocardial tracing of equidistant parallel left ventricular short-axis slices. Slicing from the 3DE data sets were done by both 2.9-mm slice thickness (method 3DE-A) and by 8 equidistant short-axis slices (method 3DE-B); for MRI analysis, 9-mm slice thickness was used. RESULTS: Analysis time required for manual endocardial tracing of end-diastolic and end-systolic short-axis slices was 10 minutes for the 3DE-B method compared with 40 minutes by the 3DE-A method. For all 40 subjects the mean +/- SD of end-diastolic LVV (mL) were 181 +/- 76, 179 +/- 73, and 182 +/- 76; for end-systolic LVV (mL), 120 +/- 76, 120 +/- 75, and 122 +/- 77; and for EF (%), 39 +/- 18, 38 +/- 18, and 38 +/- 18 for MRI, 3DE-A, and 3DE-B methods, respectively. The differences between 3DE-A and 3DE-B with MRI for calculating end-diastolic and end-systolic LVV and EF were not significant for the whole group of subjects as well as for the subgroups. The 3DE-B method had excellent correlation and close limits of agreement with MRI for calculating end-diastolic and end-systolic LVV and EF: r = 0.98 (-1.3 +/- 26.6), 0.99 (-1.6 +/- 21. 2), and 0.99 (0.2 +/- 5.2), respectively. The correlation between 3DE-A and MRI were r = 0.97, 0.98, and 0.98, and the limits of agreement were -1.4 +/- 36, -0.6 +/- 26, and 0.6 +/- 8 for calculating end-diastolic and end-systolic LVV and EF, respectively. In addition, excellent correlation and close limits of agreement between 3DE-A and 3DE-B with MRI for LVV and EF calculation was also found for the subgroups. Intraobserver and interobserver variability (SEE) of MRI for calculating end-diastolic and end-systolic LVV and EF were 6.3, 4.7, and 2.1; and 13.6, 11.5, and 4.7; respectively, whereas that for 3DE-B were 3.1, 4.4, and 2.2; and 6.2, 3.8, and 3. 6; respectively. Comparable observer variability was also found for the A and B subgroups. CONCLUSIONS: The 3DE-A and 3DE-B methods have excellent correlation and close limits of agreement with MRI for calculating LVV and EF in both normal subjects and cardiac patients. The 3DE-B method by paraplane analysis with 8 equidistant short-axis slices has observer variability similar to MRI and reduces the 3DE analysis time to 10 minutes, therefore offering a rapid, reproducible, and accurate method for LVV and EF calculation.     

The evolution of the frontal lobes: a volumetric analysis based on three-dimensional reconstructions of magnetic resonance scans of human and ape brains

Scenarios regarding the evolution of cognitive function in hominids depend largely on our understanding of the organization of the frontal lobes in extant humans and apes. The frontal lobe is involved in functions such as creative thinking, planning of future actions, decision making, artistic expression, aspects of emotional behavior, as well as working memory, language and motor control. It is often claimed that the frontal lobe is disproportionately larger in humans than in other species, but conflicting reports exist on this issue. The brain of the apes in particular remains largely unknown. In this report we measure the volume of the frontal lobe as a whole and of its main sectors (including cortex and immediately underlying white matter) in living humans, and in post-mortem brains of the chimpanzee, gorilla, orang-utan, gibbon and the macaque using three-dimensional reconstructions of magnetic resonance (MR) scans of the brain. On the basis of these data we suggest that although the absolute volume of the brain and the frontal lobe is largest in humans, the relative size of the frontal lobe is similar across hominoids, and that humans do not have a larger frontal lobe than expected from a primate brain of the human size. We also report that the relative size of the sectors of the frontal lobe (dorsal, mesial, orbital) is similar across the primate species studied. Our conclusions are preliminary, because the size of our sample, although larger than in previous studies, still remains small. With this caveat we conclude that the overall volume of the frontal lobe in hominids enlarged in absolute size along with the rest of the brain, but did not become relatively larger after the split of the human line from the ancestral African hominoid stock. Aspects other than relative volume of the frontal lobe have to be responsible for the cognitive specializations of the hominids.     

Measurement of renal vein blood flow in rats by high-field magnetic resonance

The aim of the present study was to examine whether magnetic resonance imaging (MRI) based method for non-invasive in vivo measurement of vein blood flow in rats could be used to estimate renal blood flow (RBF). Measurements were performed using a high-field (7 Tesla) MRI scanner with a short echo time phase contrast velocity measurement pulse sequence. The method was evaluated in vitro by flow measurements in an acrylic pipe and in vivo by recording left renal vein blood flow in normal and unilaterally nephrectomized rats. In a subset of animals RBF was measured by a direct method using 14C-tetraethylammoniumbromide. In vitro a high accuracy was found between applied and MRI measured flow rates in the range from 0.5 to 33 ml/min (r = 0.997; P < 0.001). In vivo the MRI measured left renal vein blood flow was 70% higher in unilaterally nephrectomized animals compared to control animals (3.4 +/- 0.4 ml/min/ 100 g body wt vs. 2.0 +/- 0.1 ml/min/100 g body wt, P < 0.001). Direct measurements of RBF revealed comparable values (3.4 +/- 0.3 ml/min/100 g body wt vs. 2.3 +/- 0.4 ml/min/100 g body wt, P = 0.05). In addition, the left kidney volume was recorded by MRI with an increase amounting to 40% (1.18 +/- 0.05 ml vs. 0.84 +/- 0.02 ml; P < 0.001) in the nephrectomized group compared to controls. Finally, a positive correlation was seen between left renal vein blood flow and MRI measured renal volume (r = 0.91; P < 0.001). In summary, MRI is a non-invasive tool by which measurement of renal vein blood flow can be performed, and it is concluded that MRI-based renal vein flow measurements can be used to estimate RBF in small rodents.     

Comparison of muscle volume between congenital and acquired superior oblique palsies by magnetic resonance imaging

A panel of 13 highly informative dinucleotide repeats which are genetic markers for 17 cytokine genes and receptors is described. The marker panel is designed for use in fluorescence based semi-automated genotyping, with primers designed and labelled such that all 13 markers can be analysed in a single lane of a gel. Cytokine and cytokine receptors have a potential role in many diseases and pathological processes. Evidence suggests that cytokine production in vivo is influenced by polymorphisms within regulatory sequences of these genes. Genetic investigation of disease genes often requires genotyping of very large numbers of individuals. This panel of markers will, therefore, provide a useful tool to those wishing to undertake family-based linkage analysis studies of cytokine genes or large-scale association studies.     

High-resolution three-dimensional magnetic resonance imaging for the investigation of knee joint damage during the time course of antigen-induced arthritis in rabbits

OBJECTIVE: To investigate the efficacy of high-resolution 3-dimensional magnetic resonance imaging (3-D MRI) with gadolinium contrast agent enhancement in monitoring soft tissue and hard tissue changes during the course of antigen-induced arthritis in rabbits, comparing the images with the final histologic outcome. METHODS: Arthritis was induced by intraarticular injection of methylated bovine serum albumin into rabbits that had been presensitized to the same antigen. MRI was carried out before and on predetermined days after the onset of inflammatory arthritis, up to day 60. At each time point, 3-D gradient-echo images were acquired. At the end of the study, the knee joints were processed for histologic study. RESULTS: Time-related inflammatory changes, such as soft tissue swelling, were seen initially, followed by a reduction in the acute swelling and a progression to hard tissue damage at later time points. The final 3-D data sets were then used to compare MR images with the histologic sections. The knee joints were sectioned in the sagittal, coronal, or transverse direction. Comparison of final images and histologic features at day 60 enabled a more complete interpretation of the MR images, allowing direct correlation of joint damage observed using the MRI technique with that seen in the final histologic analysis. CONCLUSION: Qualitative information derived from MR images correlated extremely well with histologic findings. These results indicate the great potential of MRI for noninvasive investigation of drug effects in this model of arthritis.