Accuracy and precision of patient positioning for pelvic MR-only radiation therapy using digitally reconstructed radiographs.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) has in recent years emerged as an imaging modality to drive precise contouring of targets and organs at risk in external beam radiation therapy. Moreover, recent advances in MRI enable treatment of cancer without computed tomography (CT) simulation. A commercially available MR-only solution, MRCAT, offers a single-modality approach that provides density information for dose calculation and generation of positioning reference images. We evaluated the accuracy of patient positioning based on MRCAT digitally reconstructed radiographs (DRRs) by comparing to standard CT based workflow. MATERIALS AND METHODS: Twenty consecutive prostate cancer patients being treated with external beam radiation therapy were included in the study. DRRs were generated for each patient based on the planning CT and MRCAT. The accuracy assessment was performed by manually registering the DRR images to planar kV setup images using bony landmarks. A Bayesian linear mixed effects model was used to separate systematic and random components (inter- and intra-observer variation) in the assessment. In addition, method agreement was assessed using a Bland-Altman analysis. RESULTS: The systematic difference between MRCAT and CT based patient positioning, averaged over the study population, were found to be (mean [95% CI]) -0.49 [-0.85 to -0.13] mm, 0.11 [-0.33 to +0.57] mm and -0.05 [-0.23 to +0.36] mm in vertical, longitudinal and lateral directions, respectively. The increases in total random uncertainty were estimated to be below 0.5 mm for all directions, when using MR-only workflow instead of CT. CONCLUSIONS: The MRCAT pseudo-CT method provides clinically acceptable accuracy and precision for patient positioning for pelvic radiation therapy based on planar DRR images. Furthermore, due to the reduction of geometric uncertainty, compared to dual-modality workflow, the approach is likely to improve the total geometric accuracy of pelvic radiation therapy.

Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy.

OBJECTIVE: The purpose of this prospective multicenter study was to assess the safety and technical feasibility of volumetric Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with symptomatic uterine fibroids. METHODS: Thirty-three patients with 36 fibroids were treated with volumetric MR-HIFU ablation. Treatment capability and technical feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with MR thermal dose predicted treatment volumes. Safety was determined by evaluation of complications or adverse events and unintended lesions. Secondary endpoints were pain and discomfort scores, recovery time and length of hospital stay. RESULTS: The mean NPV calculated as a percentage of the total fibroid volume was 21.7%. Correlation between the predicted treatment volumes and NPVs was found to be very strong, with a correlation coefficient r of 0.87. All patients tolerated the treatment well and were treated on an outpatient basis. No serious adverse events were reported and recovery time to normal activities was 2.3 ± 1.8 days. CONCLUSION: This prospective multicenter study proved that volumetric MR-HIFU is safe and technically feasible for the treatment of symptomatic uterine fibroids. KEY POINTS: • Magnetic-resonance-guided high intensity focused ultrasound allows non-invasive treatment of uterine fibroids. • Volumetric feedback ablation is a novel technology that allows larger treatment volumes • MR-guided ultrasound ablation of uterine fibroids appears safe using volumetric feedback.

Magnetic resonance imaging-guided diskography and diagnostic lumbar 0.23T MRI: an assessment study.

PURPOSE: To describe the in vivo appearance of magnetic resonance imaging (MRI) diskograms of normal and degenerated lumbar intervertebral disks, and to evaluate the differences in imaging findings between sequential diagnostic MRI and MRI diskography. MATERIAL AND METHODS: Nine consecutive patients underwent MRI-guided diskography in order to determine possible pain provocation during puncture and contrast medium injection. All patients had preceding clinical suspicion of lumbar diskogenic pain and findings of lumbar disk degeneration in diagnostic (MRI, computed tomography (CT), plain radiography). A 0.23T open MRI scanner with interventional tools was used for imaging and instrument guidance. On all patients, a complementary diagnostic MRI study of the lumbar spine before and after the MRI-guided disk injection was performed, and subsequent axial MRI diskograms were obtained. RESULTS: A total of 25 disk punctures were initialized, and 25 MRI diskograms were obtained and their expression described. There was a correlation between the degenerative disk findings visualized by diagnostic MRI and MRI diskograms. CONCLUSION: The use of gadolinium contrast media in MRI-guided diskography enables the evaluation of MRI diskograms. Our results suggest that MRI-guided diskography can be used to substitute conventional diskography or CT-diskography and as an augmenting method to assess diagnostic information upon degenerative processes of the lumbar spine.

MR temperature measurement in liver tissue at 0.23 T with a steady-state free precession sequence.

MRI can be used for monitoring temperature during a thermocoagulation treatment of tumors. The aim of this study was to demonstrate the suitability of a 3D steady-state free precession sequence (3D Fast Imaging with Steady-State Precession, 3D TrueFISP) for MR temperature measurement at 0.23 T, and to compare it to the spin-echo (SE) and spoiled 3D gradient-echo (3D GRE) sequences. The optimal flip angle for the TrueFISP sequence was calculated for the best temperature sensitivity in the image signal from liver tissue, and verified from the images acquired during the thermocoagulation of excised pig liver. Factors influencing the accuracy of the measured temperatures are discussed. The TrueFISP results are compared to the calculated values of optimized SE and 3D GRE sequences. The accuracy of TrueFISP in the liver at 0.23 T, in imaging conditions used during thermocoagulation procedures, is estimated to be +/-3.3 degrees C for a voxel of 2.5 x 2.5 x 6 mm(3) and acquisition time of 18 s. For the SE and GRE sequences, with similar resolution and somewhat longer imaging time, the uncertainty in the temperature is estimated to be larger by a factor of 2 and 1.2, respectively.

MR-guided core biopsies of soft tissue tumours on an open 0.23 T imager.

PURPOSE: To assess the feasibility of MR-guided soft tissue core biopsies on an open 0.23 T magnet. MATERIAL AND METHODS: Twenty-nine consecutive patients with known or suspected benign or malignant soft tissue tumours underwent MR imaging. A one-slice dynamic enhancement sequence was used to obtain an enhancement curve of the tumour. MR-guided core biopsy of the tumour was performed in the same session. RESULTS: All biopsies could be performed on an open 0.23 T magnet. Standard MR images and dynamic enhancement curves were used in deciding biopsy route and target. The MR-guided core biopsy specimens were sufficient for histopathological diagnosis in 27 of 29 cases. CONCLUSION: Open magnet configuration allows easy access to the patient and near real-time imaging guidance of soft tissue tumours. Minimally invasive MR-guided core biopsies of soft tissue tumours are feasible and help to avoid open surgical biopsies.

Registration in interventional procedures with optical navigator.

Performing interventional procedures in the close proximity to an MR scanner widens the range of operations available for an optical tracking system. In order to gain the full benefits from both unrestricted use of surgical instruments outside the magnet and intraoperative imaging, a method for transferring the registration data of the optical navigator between two locations is required. An optical tracking system, which provides such a transfer method and tracks patient position during a surgical procedure, has been developed, tested, and demonstrated with two patient cases. J. Magn. Reson. Imaging 2001;13:93-98.

Dynamic contrast-enhanced MR imaging and MR-guided bone biopsy on a 0.23 T open imager.

OBJECTIVE: To assess the feasibility of MR (magnetic resonance)-guided bone biopsies. DESIGN AND PATIENTS: Thirty-six consecutive patients with known or suspected benign or malignant bone lesions underwent comprehensive MR imaging. A dynamic contrast-enhanced sequence followed by stationary T1-weighted sequences were obtained and MR-guided bone biopsy of the tumor at the site with fastest enhancement was performed using an open 0.23 T MR imager. RESULTS: All MR-guided bone biopsies samples were estimated to be sufficient by the pathologists. The biopsy specimens were diagnostic in 34 of 36 cases. CONCLUSION: MR-guided bone biopsies combined with dynamic contrast-enhanced imaging are feasible and safe for the diagnostic investigation of equivocal bone lesions.

Nerve root infiltration of the first sacral root with MRI guidance.

The purpose of this clinical trial was to describe the methodology and evaluate the accuracy of optical tracking-based magnetic resonance (MR)-guided infiltration of the first sacral (S1) root. Thirty-five infiltrations were performed on 34 patients with a 0. 23-T open C-arm magnet installed in a fully equipped operation room with large-screen (36 inches) display and optical navigator utilizing infrared passive tracking. T1 and T2 fast spin-echo (FSE) images were used for localizing the target and fast field echo for monitoring the procedure. Saline as contrast agent in single-shot (SS)FSE images gave sufficient contrast-to-noise ratio. Twenty-four patients had unoperated L5/S1 disc herniation, and 10 had S1 root irritation after failed back surgery. Needle placement was successful in 97% of the cases, and no complications occurred. Outcome was evaluated 1-6 months (mean 2.2 months) after the procedure and was comparable to that of other studies using fluoroscopy or computed tomography guidance. MR-guided placement of the needle is an accurate technique for first sacral root infiltration.

Ability of cecropin B to penetrate the enterobacterial outer membrane.

The cationic amphipathic insect peptide cecropin B was almost as active on wild-type enteric bacteria as it was on their lipopolysaccharide and lipid A mutants that have very defective outer membrane. The polymyxin-resistant strains, which elaborate altered, less anionic lipopolysaccharide, were completely susceptible to cecropin B. No synergism was found between cecropin B and hydrophobic antibiotics. Throughout the study, the activity of cecropin B resembled that of quaternary detergents.

Susceptibility of gram-negative bacteria to the synergistic bactericidal action of serum and polymyxin B nonapeptide.

Polymyxin B nonapeptide was able to sensitize Escherichia coli strains and strains of Salmonella typhimurium, Klebsiella spp., Enterobacter cloacae, Pseudomonas aeruginosa, and Haemophilus influenzae to the bactericidal action of fresh normal human serum. The degree of sensitization varied significantly within the strains. Strains of Proteus mirabilis, Neisseria gonorrhoeae, and N. meningitidis remained resistant.

An outer membrane-disorganizing peptide PMBN sensitizes E. coli strains to serum bactericidal action.

The small cationic outer membrane-disorganizing peptide PMBN sensitized four smooth, encapsulated strains of Escherichia coli (serotypes 02:K1, 04:K12, 018:K1, and 018:K5) to the lethal action of serum. The concentrations of PMBN required were low (0.3 to 1.0 microgram/ml). One E. coli strain (IH 11030; 075:K5) remained virtually resistant to serum and also to anti-075 hyperimmune serum plus complement (C) even in the presence of PMBN. This strain was nevertheless sensitive to the outer membrane permeability-increasing action of PMBN. In the bactericidal system, PMBN could be replaced by high concentrations of lysine20 or protamine but not lysine4. The PMBN-dependent bactericidal activity of GPS was abolished by heating or zymosan treatment that inactivate its C but not by lack of the action of the classical pathway of the C in C4-deficient GPS. PMBN formed a bactericidal system also with normal rabbit, rat, and human serum but not with mouse serum. The bactericidal system against E. coli 018:K1 and its derivative EH 817 (018:K1-) was found to require a factor that can be removed from normal sera by absorption with a rough E. coli strain. This factor could be replaced by specific anti-018 antibodies. The bactericidal activity of fetal calf serum plus PMBN against E. coli 018:K1 was enhanced by normal rabbit or anti-E. coli 018 hyperimmune serum. We suggest that PMBN unshields the deep structures and the hydrophobic membrane milieu of the outer membrane and facilitates the insertion of the membrane attack complex of the C into this milieu.

Three-dimensional structure of the regularly constructed surface layer from Synechocystis sp. strain CLII.

The isolated, outermost cell wall layer from Synechocystis sp. strain CLII is described using electron microscopy and Fourier reconstruction to study the three-dimensional structure of the proteins within the layer to a resolution of ca. 3 nm. This surface layer forms regular hexagonal arrays (a = b = 15.2 nm). The two-dimensional space group is p6. The monomer proteins form hexamers arranged around a central hollow cylinder. The linkers between the hexamers are of the delta type and are located approximately in the central section between the top and bottom of the protein layer.

Polycations sensitize enteric bacteria to antibiotics.

Polymyxin B nonapeptide, a polymyxin B derivative which lacks the fatty acyl part and the bactericidal activity of polymyxin, was shown to sensitize smooth encapsulated Escherichia coli (O18:K1) and smooth Salmonella typhimurium to hydrophobic antibiotics (novobiocin, fusidic acid, erythromycin, clindamycin, nafcillin, and cloxacillin). The polymyxin B nonapeptide-treated bacteria were as sensitive to these antibiotics as are deep rough mutants. A lysine polymer with 20 lysine residues (lysine 20) had a largely similar effect. Larger lysine polymers and the protamine salmine were bactericidal but, at sublethal concentrations, sensitized the strains to the antibiotics mentioned above, whereas lysine4, streptomycin, cytochrome c, lysozyme, and the polyamines cadaverine, spermidine, and spermine had neither bactericidal nor sensitizing activity.

Polycations as outer membrane-disorganizing agents.

The outer membrane-disorganizing effect of a short (10-min) treatment with polycationic agents was studied with smooth Salmonella typhimurium used as a test organism. The polycationic agents were the protamine salmine, a lysine polymer with 20 lysine residues (lysine20), and the deacylated polymyxin B derivative polymyxin B nonapeptide. Two different types of outer membrane-disorganizing were found. Protamine and lysine20 released 20 to 30% of the lipopolysaccharide from the outer membrane and sensitized the bacteria to the anionic detergent sodium dodecyl sulfate but did not (under these conditions) make the bacteria permeable to the hydrophobic probes fusidic acid and actinomycin D. In contrast, polymyxin B nonapeptide did not release lipopolysaccharide or sensitize the bacteria to sodium dodecyl sulfate but made the outer membrane permeable to the hydrophobic probes. None of the agents was bactericidal under the conditions used or caused any leakage of periplasmic beta-lactamase. Polymyxin B was used as a reference and showed characteristic outer membrane-disorganizing action. In thin-section electron microscopy, polymyxin B nonapeptide caused the appearance of long, narrow, finger-like projections on the outer membrane. Protamine and lysine20 caused a distinctly wrinkled appearance of the outer membrane but no projections.

Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide.

A major virulence factor of bacteria that cause generalized infections is their resistance to the lytic action of the complement cascade, an important defence mechanism of the host. Invasive Gram-negative enteric bacteria, which cause about one-third of all bacteraemic infections, are completely resistant to lysis by complement, even in the presence of hyperimmune serum. The same bacteria are also resistant to many antibiotics that are effective therapeutic agents against other bacteria, as the outermost surface layer (the outer membrane) of the bacteria functions as a permeability barrier. Here we show that it is possible to sensitize such bacteria to both complement and antibiotics by using an agent that binds to the outer membrane. This agent is a nontoxic derivative of polymyxin which by itself has no bactericidal action.

Outer membrane permeability barrier disruption by polymyxin in polymyxin-susceptible and -resistant Salmonella typhimurium.

In contrast to their polymyxin-susceptible parent strains, polymyxin-resistant Salmonella typhimurium mutants (pmrA strains) did not lose their outer membrane permeability barrier to macromolecules such as lysozyme and periplasmic proteins upon polymyxin treatment. The sensitization of pmrA strains to deoxycholate-induced lysis required 10-times-higher polymyxin concentrations than did the sensitization of the parent strains. These findings indicate that the pmrA mutation affects the outer membrane and decreases its susceptibility to polymyxin. By contrast, the pmrA mutants did not differ from their parents in the uptake of gentian violet after treatment with polymyxin, suggesting a degree of specificity in the pmrA effect in the outer membrane.

Ultrastructure of the cell wall of a Synechocystis strain.

The ultrastructure of the cell wall of a Synechocystis strain, isolated from the Gulf of Finland, was studied using several electron microscopic techniques. This cyanobacterium has numerous projections which were observed to penetrate the cell wall complex. An additional layer (AL) was associated with the outer membrane. An additional external wall layer (EL) was connected to the outer membrane complex by thin fibers as revealed by ruthenium red staining. A hexagonal arrangement of the subunits in the additional external wall layer with a lattice constant of 15.5 nm was found.

Two improved methods for obtaining axenic cultures of cyanobacteria.

Scoring the agar plate before incubation under unidirectional light led to a rapid separation of gliding filamentous cyanobacteria from their contaminating bacteria. Twenty strains were purified by the method. Additionally, 13 axenic cyanobacterial strains were isolated from pour plates made after treatment of cyanobacterial cultures in tryptone-yeast extract-glucose broth with cycloserine in darkness to select for obligate photoautotrophs.

Decreased binding of polymyxin by polymyxin-resistant mutants of Salmonella typhimurium.

Polymyxin-resistant pmrA strains were shown to absorb only about 25% of the amount of polymyxin absorbed by the corresponding polymyxin-sensitive parent strains. The lipopolysaccharide from the pmrA strains bound less polymyxin than the lipopolysaccharide from the parent strains.