Three-dimensional movements of the lumbar spine facet joints and segmental movements: in vivo examinations of normal subjects with a new non-invasive method.

INTRODUCTION: Examination with CT and image registration is a new technique that we have previously used to assess 3D segmental motions in the lumbar spine in a phantom. Current multi-slice computed tomography (CT) offers highly accurate spatial volume resolution without significant distortion and modern CT scanners makes it possible to reduce the radiation dose to the patients. Our aim was to assess segmental movement in the lumbar spine with the aforementioned method in healthy subjects and also to determine rotation accuracy on phantom vertebrae. MATERIAL AND METHOD: The subjects were examined in flexion-extension using low dose CT. Eleven healthy, asymptomatic subjects participated in the current study. The subjects were placed on a custom made jig which could provoke the lumbar spine into flexion or extension. CT examination in flexion and extension was performed. The image analysis was performed using a 3D volume fusion tool, registering one of the vertebrae, and then measuring Euler angles and distances in the registered volumes. RESULTS: The mean 3D facet joint translation at L4-L5 was in the right facet joint 6.1 mm (3.1-8.3), left facet joint 6.9 mm (4.9-9.9), at L5-S1: right facet joint 4.5 mm (1.4-6.9), and for the left facet joint 4.8 mm (2.0-7.7). In subjects the mean angles at the L4-L5 level were: in the sagittal plane 14.3°, coronal plane 0.9° (-0.6 to 2.8), and in the transverse plane 0.6° (-0.4 to 1.5), in the L5-S1 level the rotation was in sagittal plane 10.2° (2.4-16.1), coronal plane 0° (-1.2 to 1.2), and in the transverse plane 0.2° (-0.7 to 0.3). Repeated analysis for 3D facet joint movement was on average 5 mm with a standard error of mean of 0.6 mm and repeatability of 1.8 mm (CI 95%). For segmental rotation in the sagittal plane the mean rotation was 11.5° and standard error of mean 1°. The repeatability for rotation was 2.8° (CI 95%). The accuracy for rotation in the phantom was in the sagittal plane 0.7°, coronal plane 1°, and 0.7 in the transverse plane. CONCLUSION: This method to assess movement in the lumbar spine is a truly 3D method with a high precision giving both visual and numerical output. We believe that this method for measuring spine movement is useful both in research and in clinical settings.

Model studies on segmental movement in lumbar spine using a semi-automated program for volume fusion.

OBJECTIVE: To validate a new non-invasive CT method for measuring segmental translations in lumbar spine in a phantom using plastic vertebrae with tantalum markers and human vertebrae. MATERIAL AND METHODS: One hundred and four CT volumes were acquired of a phantom incorporating three lumbar vertebrae. Lumbar segmental translation was simulated by altering the position of one vertebra in all three cardinal axes between acquisitions. The CT volumes were combined into 64 case pairs, simulating lumbar segmental movement of up to 3 mm between acquisitions. The relative movement between the vertebrae was evaluated visually and numerically using a volume fusion image post-processing tool. Results were correlated to direct measurements of the phantom. RESULTS: On visual inspection, translation of at least 1 mm or more could be safely detected and correlated with separation between the vertebrae in three dimensions. There were no significant differences between plastic and human vertebrae. Numerically, the accuracy limit for all the CT measurements of the 3D segmental translations was 0.56 mm (median: 0.12; range: -0.76 to +0.49 mm). The accuracy for the sagittal axis was 0.45 mm (median: 0.10; range: -0.46 to +0.62 mm); the accuracy for the coronal axis was 0.46 mm (median: 0.09; range: -0.66 to +0.69 mm); and the accuracy for the axial axis was 0.45 mm (median: 0.05; range: -0.72 to + 0.62 mm). The repeatability, calculated over 10 cases, was 0.35 mm (median: 0.16; range: -0.26 to +0.30 mm). CONCLUSION: The accuracy of this non-invasive method is better than that of current routine methods for detecting segmental movements. The method allows both visual and numerical evaluation of such movements. Further studies are needed to validate this method in patients.

Regulation of rat hepatic low density lipoprotein receptors. In vivo stimulation by growth hormone is not mediated by insulin-like growth factor I.

Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on hepatic LDL receptors are direct or mediated by insulin-like growth factor I (IGF-I). Two models were studied in which substitution with GH is important for the regulation of hepatic LDL receptors: hypophysectomized rats receiving high-dose ethynylestradiol or challenge with dietary cholesterol. The hypophysectomized rats were hormonally substituted by infusion with dexamethasone and L-thyroxine, and either GH or IGF-I. In both models, GH was essential for maintaining normal expression of LDL receptors. In contrast, despite fully normalized plasma levels, IGF-I did not support the expression of hepatic LDL receptors. Analysis of plasma lipoproteins revealed that substitution with GH, but not with IGF-I, reduced LDL and intermediate density lipoproteins. In addition, determination of hepatic mRNA levels for apo B-100 and apo B-48 indicated that GH may be more effective than IGF-I in the promotion of apo B mRNA editing. In conclusion, GH has specific effects on hepatic LDL receptor expression and plasma lipoprotein levels that are not mediated by IGF-I.

Fusion of radiostereometric analysis data into computed tomography space: application to the elbow joint.

Improvement of joint prostheses is dependent upon information concerning the biomechanical properties of the joint. Radiostereometric analysis (RSA) and electromagnetic techniques have been applied in previous cadaver and in vivo studies on the elbow joint to provide valuable information concerning joint motion axes. However, such information is limited to mathematically calculated positions of the axes according to an orthogonal coordinate system and is difficult to relate to individual skeletal anatomy. The aim of this study was to evaluate the in vivo application of a new fusion method to provide three-dimensional (3D) visualization of flexion axes according to bony landmarks. In vivo RSA data of the elbow joint's flexion axes was combined with data obtained by 3D computed tomography (CT). Results were obtained from five healthy subjects after one was excluded due to an instable RSA marker. The median error between imported and transformed RSA marker coordinates and those obtained in the CT volume was 0.22 mm. Median maximal rotation error after transformation of the rigid RSA body to the CT volume was 0.003 degrees . Points of interception with a plane calculated in the RSA orthogonal coordinate system were imported into the CT volume, facilitating the 3D visualization of the flexion axes. This study demonstrates a successful fusion of RSA and CT data, without significant loss of RSA accuracy. The method could be used for relating individual motion axes to a 3D representation of relevant joint anatomy, thus providing important information for clinical applications such as the development of joint prostheses.

A new computed tomography-based radiographic method to detect early loosening of total wrist implants.

BACKGROUND: Diagnosis of loosening of total wrist implants is usually late using routine radiographs. Switching modality to computed tomography (CT) should aid in early diagnosis. PURPOSE: To propose and evaluate the accuracy of a new CT method for assessing loosening of the carpal component in total wrist arthroplasty. MATERIAL AND METHODS: A protocol encompassing volume registration of paired CT scans of patients with unexplained pain in a prosthetically replaced wrist (used in clinical routine) is presented. Scans are acquired as a dynamic examination under torsional load. Using volume registration, the carpal component of the prosthesis is brought into spatial alignment. After registration, prosthetic loosening is diagnosed by a shift in position of the bones relative to the prosthesis. This study is a preclinical validation of this method using a human cadaverous arm with a cemented total wrist implant and tantalum markers. Seven CT scans of the arm were acquired. The scans were combined into 21 pairs of CT volumes. The carpal component was registered in each scan pair, and the residual mismatch of the surrounding tantalum markers and bone was analyzed both visually and numerically. RESULTS: The detection limit for prosthetic movement was less than 1 mm. CONCLUSION: The results of this study demonstrate that CT volume registration holds promise to improve detection of movement of the carpal component at an earlier stage than is obtainable with plain radiography.

Assessment of wear and periacetabular osteolysis using dual energy computed tomography on a pig cadaver to identify the lowest acceptable radiation dose.

OBJECTIVES: Computed tomography (CT) plays an important role in evaluating wear and periacetabular osteolysis (PAO) in total hip replacements. One concern with CT is the high radiation exposure since standard pelvic CT provides approximately 3.5 millisieverts (mSv) of radiation exposure, whereas a planar radiographic examination with three projections totals approximately 0.5 mSv. The objective of this study was to evaluate the lowest acceptable radiation dose for dual-energy CT (DECT) images when measuring wear and periacetabular osteolysis in uncemented metal components. MATERIALS AND METHODS: A porcine pelvis with bilateral uncemented hip prostheses and with known linear wear and acetabular bone defects was examined in a third-generation multidetector DECT scanner. The examinations were performed with four different radiation levels both with and without iterative reconstruction techniques. From the high and low peak kilo voltage acquisitions, polychrmoatic images were created together with virtual monochromatic images of energies 100 kiloelectron volts (keV) and 150 keV. RESULTS: We could assess wear and PAO while substantially lowering the effective radiation dose to 0.7 mSv for a total pelvic view with an accuracy of around 0.5 mm for linear wear and 2 mm to 3 mm for PAO. CONCLUSION: CT for detection of prosthetic wear and PAO could be used with clinically acceptable accuracy at a radiation exposure level equal to plain radiographic exposures.Cite this article: B. Sandgren, M. Skorpil, P. Nowik, H. Olivecrona, J. Crafoord, L. Weidenhielm, A. Persson. Assessment of wear and periacetabular osteolysis using dual energy computed tomography on a pig cadaver to identify the lowest acceptable radiation dose. Bone Joint Res 2016;5:307-313. DOI: 10.1302/2046-3758.57.2000566.

Growth hormone treatment does not alter biliary lipid metabolism in healthy adult men.

GH is important for the hepatic low density lipoprotein (LDL) receptor induction that occurs after estrogen treatment. GH treatment increases liver LDL receptors and lowers plasma LDL cholesterol in man. Estrogen treatment enhances biliary secretion of cholesterol, resulting in supersaturation of bile and an increased risk of gallstone formation. The present study was undertaken to investigate whether GH treatment also influences biliary lipid metabolism in humans. Twelve healthy male volunteers (mean age, 31 +/- 1 yr) were studied before and during the third week of treatment with recombinant human GH (0.1 IU/kg.day). Plasma lipids, bile acid kinetics, and biliary lipid composition were monitored. Plasma total and LDL cholesterol levels were reduced by 10% in response to therapy. However, no significant changes were observed in the biliary lipid composition or cholesterol saturation of gallbladder bile. Furthermore, there were no changes in chenodeoxycholic acid or cholic acid kinetics. The reduction of plasma LDL cholesterol in response to GH treatment in healthy adult men is not associated with detectable changes in biliary lipid metabolism. Thus, in contrast to estrogen, GH therapy of adults probably does not result in an increased risk of cholesterol gallstone development.

Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: serum levels and hepatic messenger ribonucleic acid responses in humans.

We investigated the acute (4-5 h) and short-term (5 days) effects of GH treatment on hepatic messenger RNA (mRNA) levels of the genes for the insulin-like growth factors (IGFs), insulin-like growth factor binding protein-1, -2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum levels of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA decreased after short-term GH treatment, without changes in IGFBP-1 or -3 expression. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the short-term group. We observed increased IGFBP-3 serum levels after 5 days of GH treatment, likely due to increased formation of the ternary complex. Our results show that the metabolic effects by GH on the IGF axis are complex. In addition to a direct stimulation of IGF-I and ALS expression, GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, possibly facilitating enhanced IGF bioavailability to target tissues.

GH is a regulator of IGF2 promoter-specific transcription in human liver.

The regulation of the insulin-like growth factor-II gene (IGF2) is complex and involves the usage of four promoters resulting in different 5' untranslated regions, but with a common translated product. The IGF2 gene product is a mitogenic and survival factor that has been suggested to be important for a normal fetal development and cancer. In this paper we present evidence suggesting that the human IGF2 gene is regulated by GH, and that this regulation occurs in a promoter-specific way. Three lines of evidence support this finding. First, in vivo data from patients treated with GH (one injection or daily injections for 5 consecutive days) showed an increase in the IGF2 P2 promoter derived transcript after acute treatment, and of the P4 promoter transcript after short-term treatment while the P1 promoter derived transcript did not show any significant change. Secondly, isolated human liver cells treated with GH for 2 h displayed an upregulation of the P2 promoter derived transcript. Thirdly, employing transfection experiments in GH-receptor positive CHO cells with P2 and P4 promoter-luciferase constructs, an upregulation by GH was evident, while a P1 promoter construct was unresponsive. We suggest that GH may be a physiological regulator of IGF2 in humans.

Comparative double-blind investigation of meglumine metrizoate, metrizamide, and iohexol in carotid angiography.

The new nonionic contrast medium iohexol (Omnipaque) was compared with its predecessor metrizamide (Amipaque) and with the conventional ionic medium meglumine metrizoate (Isopaque Cerebral) in carotid angiography using a double-blind crossover technique. The results indicated that iohexol and metrizamide caused less discomfort than the ionic medium. The circulatory effects of the three media were generally mild, and the diagnostic effectiveness was comparable when the iodine concentration was kept in the range of 280-300 mg I/ml.

Distribution of genetic variants in preneoplastic areas of colorectal tumours.

AIMS: Loss of heterozygosity (LOH) may vary almost randomly within a colorectal tumour due to the heterogeneous morphologic character of these tumours. Despite this, as a rule, single biopsies are the source of genetic material used in studies of markers important for prognosis, clinical behaviour of the disease, or susceptibility of specific tumours to different treatment modalities. METHODS: To evaluate the importance of intratumoural variation for the results of analysis of LOH and point mutations in colorectal cancer and to determine the frequency of genetic alterations in different types of pre-neoplastic areas of the tumours, 36 consecutively operated patients with colorectal cancer were studied. After fixation, specimens were mounted on large slides containing the whole tumour. The specimens were sub classified into different areas defined as normal tissue, normal tissue closely adjacent the tumour mass, adenoma, dysplasia and invasive cancer cells. These areas were dissected and subjected to DNA extraction. RESULTS: The extracted genomic DNA was studied for LOH at chromosome 5q, 17p, and 18q and for k-ras mutations. Overall, a correlation between the intratumoural degree of neoplastic progression and the frequency of LOH and k-ras mutations was seen. These correlations were significant (p<0.008) except for dysplasia/adenomatous tissue versus invasive cancer. Microsatellite instability was found in 9% of the tumours, all except one in invasive parts of the tumours. CONCLUSIONS: This study demonstrates a statistical correlation between intratumoural differences in neoplastic degree of dedifferentiation and genetic instability in terms of LOH and point mutations of the k-ras gene in colorectal carcinoma. The importance of a careful dissection in order to localise the region with the highest probability of genetic aberrations and multiple biopsing must not be neglected. The observation that the prevalence of k-ras mutations and LOH are correlated to the degree of dedifferentiation within a colorectal tumour is in line with the concept that selected cell clones are responsible for the neoplastic progression of the tumour.

The hollow skull: a sign of brain death in Tc-99m HM-PAO brain scintigraphy.

The advantage of Tc-99m HM-PAO, a newly introduced compound for brain perfusion imaging, is illustrated in three patients with suspicion of brain death. With Tc-99m HM-PAO, the carotid flow study is not essential, as it is in the Tc-99m pertechnetate carotid angiogram; planar images are equally useful; and there is no need for SPECT images. For the diagnosis of brain death, Tc-99m HM-PAO can be injected in the intensive care unit and planar images can be obtained at a later time using a mobile camera or whenever the patient can be moved to the nuclear medicine department.

Effects of growth hormone on low-density lipoprotein metabolism.

GH appears to play an important role in mediating the increase in hepatic LDL receptor expression that occurs in response to pharmacological oestrogen treatment. Furthermore, in normal individuals there is evidence of an increased number of hepatic LDL receptors in response to GH, resulting in an accelerated elimination rate of the LDL particle and a subsequent lowering of LDL cholesterol. Further studies on lipoprotein metabolism in patients with GH deficiency, and also in patients with hypercholesterolaemia, would therefore be of interest.

Computed tomography analysis of radiostereometric data to determine flexion axes after total joint replacement: application to the elbow joint.

Kinematic analysis for in vivo assessment of elbow endoprostheses requires knowledge of the exact positions of motion axes relative to bony landmarks or the prosthesis. A prosthesis-based reference system is required for comparison between individuals and studies. The primary aim of this study was to further develop an earlier described algorithm for fusion of radiostereometric analysis (RSA) data and data obtained in 3D computed tomography (CT) for application to the elbow after total joint replacement. The secondary aim was to propose a method for marking of prostheses in 3D CT, enabling definition of a prosthesis-based reference system. Six patients with elbow endoprostheses were investigated. The fusion of data made it possible to visualize the motion axes in relation to the prostheses in the 3D CT volume. The differences between two repeated positioning repetitions of the longitudinal prosthesis axis were less than 0.6 degrees in the frontal and sagittal planes. Corresponding values for the transverse axis were less than 0.6 degrees in the frontal and less than 1.4 degrees (in four out of six less than 0.6 degrees ) in the horizontal plane. This study shows that by fusion of CT and RSA data it is possible to determine the accurate position of the flexion axes of the elbow joint after total joint replacement in vivo. The proposed method for implant marking and registration of reference axes enables comparison of prosthesis function between patients and studies.