Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.     

Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins

Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.     

BookReviews

Annals of Vascular Surgery -     

Percent spinal canal compromise on MRI utilized for predicting the need for surgical treatment in single-level lumbar intervertebral disc herniation

BACKGROUND CONTEXT: There is limited information describing the correlation between the initial quantitative measurements on magnetic resonance imaging (MRI) scans of disc herniation area, canal cross-section areas, percent canal compromise, and disc herniation location to the need for surgery. PURPOSE: Our aim is to determine if the size of disc herniation area, canal cross-section area, percent canal compromise, and disc herniation location taken from MRI images of patients with symptomatic single-level lumbar herniated intervertebral discs upon initial presentation to a spine surgeon, were predictive of the need for surgical treatment. STUDY DESIGN/SETTING: This is a retrospective case matched study of patient MRI images in the senior author's private practice. PATIENT SAMPLE: From a pool of 332 patients with sciatica caused by lumbar intervertebral disc herniations at our institution, 65 patients had surgery, of which MRI images were available and analyzed on 44 patients. Forty-four additional patients were randomly selected from the remaining 267 original group as nonoperative controls. METHODS: The axial MRI image showing the largest canal compromise by the herniated disc was selected for measurements. Using T1- and T2-weighted images, the areas of interest were digitally scanned at high resolution. The canal area and disc herniation area measurement were calculated from the total number of pixels per cross-sectional area, multiplied by a scan correction factor, mm(2) /pixel. Disc herniation locations were classified into either central or paracentral. The percent canal compromise was obtained by disc herniation area divided by canal cross-section area and multiplied by 100. RESULTS: The surgical group's overall mean herniated disc area was 219.6 square millimeter (mm(2)), 179.8 at L4-5, and 267.4 at L5-S1. The nonoperative group's overall mean herniated disc area was 178.4 mm(2), 135.1 at L2-3, 160.3 at L4-5, and 207.4 at L5-S1. The surgical group's overall mean canal cross-sectional area was 471.8 mm(2), 418.6 at L4-5, and 535.6 at L5-S1. The nonoperative group's overall mean canal cross-sectional area was 541.3 mm(2), 518.1 at L2-3, 446.8 at L4-5, and 669.9 at L5-S1. The overall percent canal compromise ratio in the surgery group was 46.7%, 44.1% at L4-5, and 49.8% at L5-S1. The overall percent canal compromise in the nonoperative group was 34.2%, 34.1% at L2-3, 36.1% at L4-5, and 31.8% at L5-S1. The percent canal compromise in central herniations at L4-5 level was 53.0% in the surgical group, and 32.8% in the nonoperative group; at the L5-S1 level surgical group percent canal compromise was 64.1% and in the nonoperative group canal compromise was 27%. L4-L5 level paracentral herniations canal compromise was 36.7% in the surgical group compared with 42.5% canal compromise in the nonoperative group. At the L5-S1 level the canal compromise was 45% in the surgical group and 34.8% in the nonoperative group. CONCLUSIONS: Our findings show a trend for patients treated with surgery to have larger disc herniation areas and smaller canal cross-section areas, corresponding to larger percent canal compromise than the nonoperative group. Centrally located herniations followed this trend closely at all levels studied. However, the paracentral herniation at the L4-5 level does not follow this trend, possibly because paracentral disc herniation clinical course is determined more by herniation location rather than the overall herniation size.     

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner.

A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized.     

The role of descending venography in the management of patients with chronic venous disease of the lower extremity.

The purpose of this paper is to evaluate the efficacy and clinical information obtained from the authors' first 17 consecutive descending venograms. All 17 patients had chronic venous disease refractory to standard conservative and surgical measures. The standard classification of valvular insufficiency was used in evaluating these venograms. There were no deaths, slight morbidity and minimal patient discomfort. In 16 patients meaningful clinical information was derived from the venograms, with 7 patients having deep venous valvular surgery. Descending venography will demonstrate the site of incompetent valves and estimate the degree of reflux. This test is necessary before anticipated reconstruction of deep vein valves.     

Corticosteroids for multiple sclerosis: II. Application for disease-modifying effects

Physicians who treat multiple sclerosis (MS) face the challenge of patients exhibiting ongoing disease activity, including exacerbations, loss of functional capabilities, intellectual decline, and radiologic progression, despite being on a disease-modifying agent (DMA). After searching for factors that might at least in part explain these changes—such as nonadherent drug-taking behavior, or the presence of interfer-on-neutralizing antibodies—some providers may ultimately decide to switch the patient to another DMA. In most circumstances, patients likely derive only partial effects from these agents, even in the absence of compromising factors. Thus, a number of factors must be considered in order to intensify the treatment regimen in response to disease progression. In the context of an inadequate treatment response to a DMA, some clinicians will convert the patient to an alternative therapy, and others will instead use a second agent in combination with the first (the so-called platform agent). In the first of this two-part series, we explored the use of anti-inflammatory CS and ACTH to treat MS exacerbations. Although we underscored the limited availability of evidence-based studies to support specific regimens for this purpose, there is an even greater paucity of data to support the routine use of these agents in order to achieve chronic disease-modifying effects in those who continue to deteriorate clinically, radiographically, or both. Without doubt, a number of factors influence the formulation of combination treatment plan for MS. Nevertheless, we will focus on the rationale and practical schemes that can be considered for using corticosteroids (CS) (and perhaps even ACTH) in an attempt to modify various domains of ongoing disease activity.